GRID Therapy for Extremity Soft Tissue Sarcoma

Study Overview
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Brief Summary
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Patients with extremity soft tissue sarcoma (STS) are at high risk of recurrence. Pre-operative radiotherapy is used to increase the safe removal of tumors and improve local control in these patients. Increasing the preoperative radiotherapy dose with standard techniques might lead to normal tissue toxicity and postoperative wound complications. GRID radiation therapy is a technique that may increases radiation dose with minimal added toxicity. It is hypothesized that GRID radiation dose will improve tumor response without increasing post-operative wound complications. While GRID has been used in many patients, there have been few formal studies to evaluate the safety and efficacy of the technique. In this study, a single priming dose of GRID will be administered to subjects with high-risk extremity soft tissue sarcoma prior to standard radiotherapy and tumor resection to determine the safety and clinical efficacy of the GRID dose. This single-arm pilot study will assess the safety of spatially fractionated grid radiation therapy (GRID) on 20 subjects with resectable extremity soft tissue sarcoma, followed by standard-of-care conventional radiotherapy (XRT) and tumor resection.

Official Title
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Safety, Efficacy, and Mechanism of Pre-operative Spatially Fractionated GRID Radiation Therapy in Patients With Extremity Soft Tissue Sarcoma: A Pilot Study

Conditions
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Sarcoma

Intervention / Treatment
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* Radiation: GRID therapy


Participation Criteria
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Eligibility Criteria
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In order to participate in this study a subject must meet all of the eligibility criteria outlined below. Inclusion Criteria: Written informed consent was obtained to participate in the study and HIPAA authorization for the release of personal health information. Subjects are willing and able to comply with study procedures based on the judgment of the investigator. Age ≥ 18 years at the time of consent. Eastern Cooperative Oncology Group (ECOG) Performance status of 0 - 2 (Karnofsky Performance Status equivalent of 50 - 100). Histological or cytological evidence/confirmation of extremity soft tissue sarcoma as determined by core-needle biopsy or excision biopsy. If the diagnostic tissue is not available or sufficient to perform correlative studies, must be willing to provide the mandatory pre-treatment core-needle biopsy. In some cases of extremity STS, subjects undergo an attempted surgical resection for a presumed benign condition and the specimen reveals malignancy. Such subjects are allowed so long as a complete, oncologic, resection was not performed/attempted and there is ≥ 5 cm of the remaining primary tumor. Exclusion Criteria: Subjects meeting any of the exclusion criteria listed below at baseline will be excluded from the study. Subjects who have received prior radiotherapy to the tumor site. Subjects who have undergone complete tumor resection of the primary tumor or who have developed tumor recurrence after resection. History of serious or non-healing wound, ulcer, or bone fracture in the treatment limb within the last 5 years. History of clinically significant lymphedema in the treated limb. History of lupus, scleroderma, Sjogren's syndrome, Ehlers-Danlos syndrome (any type), or other collagen vascular disease that may pose a relative contraindication, due to increased risk of skin or soft tissue toxicity, with radiation.

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: Fractionated grid radiation therapy<br>Subjects with resectable extremity soft tissue sarcoma received neoadjuvant grid radiation therapy (GRID), followed by standard-of-care conventional radiotherapy (XRT) and tumor resection. | Radiation: GRID therapy<br>* GRID therapy delivers a high dose of radiation to small areas of tumor interleaved with areas that intentionally receive a low dose<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Grade 2 or higher post-operative wound complications after GRID-3 months | Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The tumor specimen of the surgery | The effect of GRID on tumor response will be measured using the tumor specimen of the surgery. The major pathological response (MPR) rate will be defined as the viable residual tumor in 10% or less of the resection specimen. | At the time of surgery (Approximately 17th week) | 
| Grade 2 or higher post-operative wound complications after GRID-6 months | Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | 3 months to 6 months | 
| Long Term Safety | Safety will be quantified as the incidence of Grade 2 or higher post-operative wound complications after GRID, the standard of care XRT, and surgery. Wound complications will be graded according to The NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. CTCAE is a descriptive terminology that can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | 6 months after completrion of radiotherapy | 
| The comparative effect of GRID | The comparative effect of GRID will be quantified using histopathologic substrates. Comparisons will be made between pre-treatment biopsies, biopsies taken from different dose regions of the tumor specimen following GRID, and samples of the surgically resected tumor. The viable tumor rate will be compared. | At the time of surgery (Approximately 17th week after completion of radiotherapy) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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extremity, radiation, GRID, surgery, preoperative