Stereotactic Radiation Therapy for Pediatric Sarcomas

Study Overview
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Brief Summary
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The stereotactic body radiation therapy (SBRT) literature focuses on clinical outcomes in the adult population. However, SBRT has a particularly strong rationale for application in pediatrics given that high biologically effective doses have been shown to increase control in histologies, such as sarcoma, which are common in the pediatrics population. With stereotactic radiation therapy techniques, a reduction in normal tissue dose surrounding the target lesion of interest may also be accomplished resulting in lower toxicity. Given that pediatric patients with sarcomas, presenting with limited metastases in lung and bone, are still considered to be a curable population with aggressive local therapy, SBRT could have a significant impact on outcomes in oligometastatic patients who may be otherwise unresectable.

Detailed Description
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Pediatric patients with sarcoma who have limited metastases are still potentially curable with aggressive local therapy. However, conventional moderate dose radiation is unlikely to provide durable local control. Given the recent technologic advances in radiation delivery, it is now possible to deliver tumoricidal doses, using stereotactic radiation over a short time course with highly focal techniques. Stereotactic radiation has proven efficacious in the intracranial setting and in multiple extracranial sites in adults. It has not yet been well studied in the pediatrics population where there is a particularly strong rationale due to the ablative doses that can be delivered to tumor while simultaneously reducing high dose to normal tissues. The proposed trial is a single arm phase II study to determine the efficacy of SBRT in pediatric sarcomas with surgically unresectable metastatic disease. Oligometastatic sites eligible for treatment in this study include bony sites of disease. SBRT will be delivered to each eligible site to a total dose of 4000 delivered in 5 fractions of 800 per fractions each day. Following completion of SBRT, patients will undergo treatment response assessment with the use of diagnostic imaging, clinical examination, and completion of the Brief Pain Inventory to assess quality of life. The primary objective of this study is to determine the efficacy of SBRT delivered to a dose of 4000 centigray (cGy) in 5 fractions of 800 cGy each for patients greater than 3 years of age and < 40 years of age with metastatic disease of bone secondary to pediatric sarcoma. The secondary objectives of this study include describing the toxicity of SBRT with this regimen; assessing clinical response rate of each target lesion; assessing long-term clinical outcomes; and assessing quality of life following completion of treatment. For patients with potentially curable oligometastatic disease, surgical resection in conjunction with systemic therapy remains the standard of care. Patients on this study will continue to receive chemotherapy outside of the 2 week window for SBRT. Issues that may limit participation include our inability to assess late effects that may not develop till at least 10 years after therapy. For this reason, we will limit the population in this study to patients who are surgically unresectable and would be otherwise incurable with current standard systemic therapies.

Official Title
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A Phase II Study of Hyperfractionated Stereotactic Radiotherapy in the Treatment of Metastatic Pediatric Sarcomas of Bony Sites

Conditions
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Sarcoma, Metastatic Disease, Bony Sites

Intervention / Treatment
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* Radiation: SBRT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: histologically or cytologically confirmed metastatic sarcoma of the soft tissue or bone must have measurable disease disease must be surgically unresectable as determined by a tumor board or surgeon greater than 3 years of age less than or equal to 40 years of age life expectancy of at least 9 months adequate performance status (Lansky Performance Status greater than or equal to 50). ability to understand and willingness to sign informed consent document Exclusion Criteria: patients who have had chemotherapy or radiotherapy within 2 weeks prior to entering the study patients who have had any prior radiotherapy to the treatment site(s) patients may not participate on any other treatment protocol while they are receiving treatment on this protocol and for up to 3 months after these protocol treatments have ended pregnant women refusal of women of child bearing potential to take a pregnancy test prior to treatment

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 40 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: Hypofractionated SBRT<br>800 cGy delivered in 5 fractions every day to total dose of 4000 cGy | Radiation: SBRT<br> <br> * Other names: Stereotactic Body Radiation Therapy (SBRT);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lesion-specific Local Control at 6 Months Post-SBRT as Assessed by Percentage of Lesions Locally Controlled | Local control was defined as the absence of local progression. Local progression was defined as: (1) the development of a new soft tissue mass ≥1 cm at a site without a soft tissue component or with a soft tissue component <1 cm in at baseline (2) an increase in the largest axial dimension of the soft tissue component by >20% in lesions with a ≥ 1 cm in soft tissue component at baseline (3) a previous bone metastasis that was avid on fluorodeoxyglucose (FDG)-positron emission tomography (PET), became non-avid after SBRT, and then became avid again. The Kaplan-Meier method was used. | 6 months post-SBRT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient-specific Local Control at 6 Months Post-SBRT as Assessed by the Percentage of Patients Locally Controlled | Patient-specific local control was calculated using the Kaplan-Meier method from initiation of SBRT to time of local failure. Patients who did not experience local failure were censored at the time of last follow up. | 6 months post-SBRT | 
| Percentage of Patients With Progression-free Survival at 6 Months Post-SBRT | To assess long-term clinical outcomes of this patient population after completion of SBRT by measuring progression-free survival. The Kaplan-Meier method was used to determine progression-free for survival from initiation of SBRT to progression (local or distant) or death due to any cause. Patients that did not have evidence of progression or who did not die, where censored at the time of last follow up. | 6 months post-SBRT | 
| Percentage of Patients With Overall Survival at 6 Months Post-SBRT | The Kaplan-Meier method was used to calculate overall survival from initiation of SBRT to death due to any cause. Patients who had not died at the time of the analysis were censored at the time of last follow up. | 6 months post-SBRT | 
| Change in Quality of Life (QoL) as Assessed by the Brief Pain Inventory | Quality of life was assessed using the Brief Pain Inventory (BPI) form which assesses the severity of pain and impact on functioning on an 11-point scale at each follow up visit. Paired sample Wilcoxon signed-rank tests were performed to assess changes in pain scores on the Brief Pain Inventory; 0 being no pain and 10 being the worst pain. | Baseline and one-month post-SBRT | 
| Number of Participants Experiencing Toxicity of SBRT | To describe the toxicity of SBRT delivered to study patients measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | 12 months after treatment starts | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stereotactic, Radiotherapy, Hypofractionated