Randomised Trial of Volume of Post-operative Radiotherapy Given to Adult Patients With eXtremity Soft Tissue Sarcoma

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Giving radiation therapy after surgery may kill any tumor cells that remain after surgery. It is not yet known whether giving radiation therapy to a smaller area of tissue surrounding the tumor is as effective as giving radiation therapy to a wider area of tissue surrounding the tumor in treating soft tissue sarcoma. PURPOSE: This randomized phase III trial is studying giving external-beam radiation therapy to a small area of tissue surrounding the tumor to see how well it works compared with giving external-beam radiation therapy to a wider area of tissue surrounding the tumor in treating patients who have undergone surgery for soft tissue sarcoma of the arms, hands, legs, or feet.

Detailed Description
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OBJECTIVES: Primary Determine if reduced volume adjuvant radiotherapy increases limb function without compromising local control in patients with previously resected extremity soft tissue sarcoma. Secondary Determine the toxicity of this regimen in these patients. Determine the overall level of disability in patients treated with this regimen. Determine the disease-free survival and overall survival of these patients. OUTLINE: This is a randomized, controlled, prospective, multicenter study. Patients are stratified according to tumor grade (1 vs 2 vs 3), adequacy of surgical clearance (R0 vs R1), and treatment center. Patients are randomized to 1 of 2 treatment arms. Arm I (control): Patients undergo external beam radiotherapy (EBRT), including full margins, once daily 5 days a week for 6½ weeks . Arm II: Patients undergo EBRT as in arm I but only reduced margins are included. After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter. Peer Reviewed and Funded or Endorsed by Cancer Research UK PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study.

Official Title
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Randomised Trial of Post-Operative Radiotherapy Given to Adult Patients With Extremity Soft Tissue Sarcoma [VORTEX]

Conditions
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Sarcoma

Intervention / Treatment
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* Radiation: radiotherapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed 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 No lesions of the chest wall arising adjacent to the scapula but not originating in the shoulder bone 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 Imaging and pathology from first surgery are required Has undergone surgical resection of the tumor within the past 12 weeks No macroscopic tumor in situ after surgery Microscopically irradical surgical margin allowed Excisional biopsy with positive margins or other inadequate surgery (macroscopically involved margins) allowed only after further definitive re-excision Positive margins and no further surgery possible except amputation or major functional loss allowed provided no macroscopic residual disease is present Local recurrence within 3 months of prior surgery (or other treatment) allowed provided patient undergoes subsequent re-excision No diagnosis of any of the following: Rhabdomyosarcoma (alveolar or embryonal) Primitive neuroectodermal tumor Soft tissue Ewing's sarcoma Extraskeletal osteosarcoma Aggressive fibromatosis (desmoid tumors) Dermatofibrosarcoma protuberans Gorlin's syndrome No regional nodal disease or unequivocal distant metastasis PATIENT CHARACTERISTICS: Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception during and for 3 months after completion of study treatment No other major medical illness that would preclude study treatment No other malignancy except adequately treated nonmelanomatous carcinoma of the skin or in situ carcinoma of the cervix PRIOR CONCURRENT THERAPY: See Disease Characteristics No prior radiotherapy to the local site No prior neoadjuvant or adjuvant chemotherapy

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 120 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Control arm<br>Radiotherapy Conventional treatment arm A total of 33 fractions each of 2Gy should be given once a day for 5 days per week over 6 weeks and 3 days in week 7, totalling 66Gy. The first 50 Gy in 25 fractions will be given to CTV1 and subsequent 16 Gy in 8 fractions will be delivered to CTV2. | Radiation: radiotherapy<br>* radiotherapy as adjuvant treatment for adults with soft tissue sarcoma extremities<br>|
| Experimental: Research arm<br>Radiotherapy Research arm A total of 33 fractions each of 2Gy should be given once a day for 5 days per week over 6 weeks and 3 days in week 7, totalling 66Gy. The 66Gy in 33 fractions will be delivered to CTV2 alone. No attempt will be made to include drain/biopsy sites or the surgical scar. | Radiation: radiotherapy<br>* radiotherapy as adjuvant treatment for adults with soft tissue sarcoma extremities<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Limb functionality as measured by the Toronto Extremity Salvage Score (TESS) |  | 2 years | 
| Time to local recurrence |  | time from randomisation into the trial to the occasion when a local recurrence is confirmed by biopsy. For those patients who are not observed to have a local recurrence during the course of the study, the time to local recu | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Soft tissue and bone toxicity as measured by RTOG |  | 2 years | 
| Disease-free survival |  | defined in whole days as time from randomisation into the trial to either local or distant recurrence or death (whichever occurs first). | 
| Overall survival |  | defined in whole days as time from randomisation into the trial to death. | 
| Overall level of disability as measured by the TESS questionnaire |  | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult liposarcoma, recurrent adult soft tissue sarcoma, stage I adult soft tissue sarcoma, stage II adult soft tissue sarcoma, stage III adult soft tissue sarcoma, adult synovial sarcoma, adult angiosarcoma, adult epithelioid sarcoma, adult extraskeletal chondrosarcoma, adult leiomyosarcoma, adult malignant fibrous histiocytoma, adult malignant hemangiopericytoma, adult malignant mesenchymoma, adult fibrosarcoma, adult neurofibrosarcoma, adult alveolar soft-part sarcoma