Study of SBRT Efficacy on Intra and Extra -Cranial Tumors or Metastasis in Pediatrics Population (SBRT Pediatrics)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy of hypofractionated stereotactic radiation treatments (SBRT) on children, teenagers and young adults malignant tumors.

Detailed Description
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SBRT (Stereotactic Body Radiation Therapy) is a radiotherapy treatment which involves the delivery of a single high dose radiation treatment or a few fractionated radiation treatments (usually up to 5). A high potent biological dose of radiation is delivered to the tumor improving the cure rates for the tumor, in a manner previously not achievable by standard conventional radiation therapy. For adult patients, the Haute Authorité de Santé (HAS) validates some indications for this treatment which are the followings : Few primary or secondary brain tumors, which cannot be surgically removed Spinal tumors Primary bronchopulmonary tumors T1 T2 N0 M0 and pulmonary metastasis with slow growth and controled primary tumor. For pediatrics patients, no indication is now validated by HAS. Indications validated for adults are rare in pediatrics but not exceptional, and in such cases efficient alternative treatments does not exist. In consequence, and regarding the good results obtained in adult patients, it seems very important to validate the efficacy of this treatment on pediatrics population

Official Title
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Hypofractionated Stereotactic Radiation Treatments (SBRT) on Children, Teenagers and Young Adults Malignant Tumors

Conditions
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Brain Metastasis, Spinal Tumors, Lung Tumors, Ependymoma

Intervention / Treatment
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* Radiation: SBRT treatment


Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA: 18 months ≤ age ≤ 20 years Malignant primary tumor, histologically or cytologically proven Systemic disease under control or with slow evolution Written indication of SBRT according to local pediatrics meeting and national Radiotherapy (RT) web conference Performance Status ≤ 2 according to Eastern Cooperative Oncology Group (ECOG) Sites Brain metastasis (≤ 3 on MRI) not suitable for surgery, without hemorrhage, less than 3 cm each, not in the brain stem Primary or secondary spinal/para spinal metastasis (≤ 3), not suitable for surgery or with a non operable macroscopic residue, less than 5 cm Lung metastasis (≤ 3), less than 5 cm, not eligible for surgery, or macroscopic residue not suitable for surgery Previously irradiated relapsing isolated primitive/secondary tumor (intra cranial or extra cranial), with no possible surgery, or macroscopic residue. Affiliation to a social security scheme Signed Informed consent by patient or parents and patient IN ADDITION FOR RELAPSING EPENDYMOMA: Histologically proven local ependymoma at diagnosis Previously irradiated ependymoma Exclusive local relapse in previously irradiated site Review of operability at time of relapse by a multidisciplinary staff Relapse must be confirmed by a neuro-oncology multidisciplinary staff, on MRI evolutivity characteristics Time to relapse after previous irradiation ≥ 1 year NON-INCLUSION CRITERIA : Concomitant chemotherapy No evaluable target (except for completely resected ependymomas) Pregnancy Follow-up impossible IN ADDITION FOR RELAPSING EPENDYMOMAS: Metastatic patient at diagnosis and/or at relapse Complete remission never obtained NON-RANDOMIZATION DOSIMETRIC CRITERIA (ONLY FOR EPENDYMOMA) Cumulative doses to brain stem ≥ 115 Gy Tumor volume at relapse ≥ 30 cm3 Primary RT dose + Re-irradiation dose more than 112 Gy Cumulative dose to the chiasma > 54 Gy Cumulative dose to any point of the brain > 115 Gy

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 20 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: SBRT treatment<br>According to the site to irradiate and to local constraints, SBRT consist in 1 to 8 fractions of 5 to 18 Gy | Radiation: SBRT treatment<br>* For Brain metastasis the SBRT treatment consists on 3 fractions of 8 Gy or 5 fractions of 7 Gy or 1 fraction of 18 Gy for a single metastasis which is less than 20 mm. For primary or secondary pulmonary tumors the SBRT treatment consists on 3 fractions of 15 Gy or 5 fractions of 10 Gy for peripheral lesions and on 5 fractions of 8 Gy for proximal lesions. For primary or secondary spinal or para-spinal tumors the SBRT treatment consists on 3 fractions of 9 Gy or 5 fractions of 7 Gy. For previously irradiated tumors (same locations) the SBRT treatment consists on 5 to 8 fractions of 5 Gy. For relapsed Ependymoma previously irradiated the SBRT treatment will be allocated by surgical stratified randomization and consists on either 3 fractions of 8 Gy or 5 fractions of 5 Gy.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of SBRT assessed 6 months after treatment | The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria (complete response + partial response + stable disease) | 6 months after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of SBRT assessed between 1,5 and 3 months after treatment | The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to RECIST version 1.1 criteria (complete response + partial response + stable disease) between 1,5 and 3 months after treatment | Between 1,5 and 3 months after inclusion | 
| Progressive Free Survival | Calculated from the date of inclusion to the date defined as the first documented disease progression, or second cancer appearance, or death from any cause (Up to 5 years since the first inclusion) | From the date of inclusion to the date of progression | 
| Overall Survival | Calculated from the date of inclusion to the date of death from any cause (Up to 5 years since the first inclusion) | From the date of inclusion to the date of death (Up to 5 years since the first inclusion) | 
| Short time Safety profile of SBRT | Toxicities appeared during SBRT treatment and up to 3 months after SBRT. Toxicities will be assessed by the evaluation of intensity and incidence of the Adverse Events (AE) displayed by patients. The intensity of each AE will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | From inclusion to 3 months after inclusion | 
| Long term Safety profile of SBRT | Toxicities appeared after 24 months after inclusion. The outcome measure concerns toxicities appeared after the study following period. Toxicities will be assessed by the evaluation of intensity and incidence of the Adverse Events (AE) displayed by patients. The intensity of each AE will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | after 24 months after inclusion | 
| Efficacy of SBRT assessed 12 months after treatment | The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to RECIST version 1.1 criteria (complete response + partial response + stable disease) at 12 months after treatment | 12 months after inclusion | 
| Efficacy of SBRT assessed 24 months after treatment | The treatment efficacy is assessed by calculation of local control rate of irradiated locations according to RECIST version 1.1 criteria (complete response + partial response + stable disease) at 24 months after treatment | 24 months after inclusion | 
| Medium time Safety profile of SBRT | Toxicities appeared between 3 months and 24 months after treatment. Toxicities will be assessed by the evaluation of intensity and incidence of the Adverse Events (AE) displayed by patients. The intensity of each AE will be classified according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 | Between 3 months and 24 months after inclusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatrics, SBRT, Brain metastasis, Pulmonary metastasis, Spinal metastasis, Pulmonary primary tumor, Spinal primary tumor, Relapsed ependymoma, Relapsed irradiated tumors, Local control rate, Safety, Overall survival, Progression Free Survival