Musculoskeletal Tumors, Rhabdomyosarcoma, Sarcoma, Ewing's, Soft Tissue Sarcoma
Conditions
Keywords
Sarcoma, radiation therapy, Other musculoskeletal tumors
Brief summary
Researchers at St. Jude Children's Research Hospital are looking for more effective ways to deliver radiation therapy to pediatric tumors of the bone and soft tissues. The goal of the study is to improve local control of musculoskeletal tumors with image-guided radiation therapy (IGRT) while minimizing radiation related side effects. IGRT uses computed tomography (CT), magnetic resonance imaging (MRI) and positron emission tomography (PET) images to precisely define tumor location and to carefully plan radiation treatment. This approach allows doctors to deliver highly conformal radiation therapy to the tumor while protecting nearby healthy normal tissues.
Detailed description
The study focuses on the following primary Objectives: * To estimate local control rates with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST). * Prospectively establish a baseline estimate of local control for patients with MST (Ewing's sarcoma family of tumors (ESFT), rhabdomyosarcoma (RMS) and non-rhabdomyosarcoma soft tissue sarcoma (STS)) treated with image guided radiation therapy. * Demonstrate that the increased level of conformality afforded by image guided radiation therapy does not reduce its efficacy relative to previously utilized non-image guided radiation therapy techniques in patients with Ewing's sarcoma family of tumors, resected soft tissue sarcomas, and group III rhabdomyosarcomas. * Assess local and regional patterns of failure for patients with MST treated with image guided radiation therapy relative to their targeted volumes. * Provide a long term (\>5 year) estimate of local disease control for patients with MST (Ewing's sarcoma family of tumors (ESFT)), rhabdomyosarcoma (RMS), and non-rhabdomyosarcoma soft tissue sarcoma (STS) treated with image guided radiation therapy. The study focuses on the following secondary objectives: * Establish a quantitative baseline estimate of radiation dose-related changes in normal tissues using novel objective measures of somatic change, musculoskeletal function, tissue biochemistry and physiology. o Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations including: * Prospectively investigate whether an age based radiotherapeutic threshold of dose and volume that will induce premature physis closure and alter long bone length can be quantitatively identified. * Quantitatively explore the impact of radiation on cortical bone thinning and long bone curvature. * Relate radiation dose and volume to late (10+ year) alterations in bone integrity. * Describe the severity and time course of radiation-induced changes in the soft tissues including muscle. * Delineate sequential changes in muscular volume, muscle function and organ function (delineated by imaging and measures of physical function) following image guided radiation for specific muscular groups. * Correlate the temporal changes in muscular volume and function with changes in vascularity and metabolism defined by imaging studies.
Interventions
RADIATIONimage-guided radiotherapy
Conformal limited image radiotherapy is radiation therapy that targets tumors with a prescribed dose of radiation which allows the surrounding normal tissues to remain basically untreated.
Sponsors
St. Jude Children's Research Hospital
Lance Armstrong Foundation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 25 Years
Healthy volunteers
No
Inclusion criteria
* Age less than or equal to 25 years (new enrollments only). No age limit on participants who reconsent or reenroll. * Musculoskeletal tumor involving the primary site of origin requiring definitive, pre-operative or post-operative irradiation to that primary site. * No prior therapeutic irradiation at the primary site except for emergent radiation to the primary site lasting 1 week or less (5 treatment days) that can be dosimetrically accounted for in the analysis. * Negative serum or urine beta-HCG for females of child bearing age. * Patients will be stratified into 2 groups for evaluation of secondary objective endpoints based on the absence or presence of metastatic disease. * Patients may enter this study in specific clinical situations often defined by multimodality protocols that include the use of radiation therapy, including irradiation alone or combined with surgery (following surgical resection that may be macroscopically complete or incomplete, with positive or negative histologic margins) and/or chemotherapy (following neoadjuvant chemotherapy or combined with post-irradiation adjuvant chemotherapy).Patients requiring regional nodal irradiation and/or metastatic site irradiation are allowed as long as the primary site requires radiation.Patients with recurrent tumors or second malignant neoplasms are allowed on this study if the current primary tumor site requiring irradiation has not previously been irradiated. The treatment plan detailed in this study will allow most patients to be concurrently enrolled on institutional and COG studies. * Patients enrolled prior to amendment 4.0, who are still in active participation will be reconsented to the current version of the protocol (5.0).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Local Failures at 5 Years in Patients With Image Guided Radiation Therapy | 5-years follow-up after completion of therapy. | The cumulative incidence of local failures is used to report the control of local failures in patients with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST). |
| Cumulative Incidence of Local Failures at 10 Years in Patients With Image Guided Radiation Therapy | 10- years follow-up after completion of therapy | The cumulative incidence of local failures is used to report the control of local failures in patients with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Growth Rate and Length of Bone, Bone Density, Development of Muscle (Muscle Function, e.g. Range of Motion), Occurrence of Organ Specific (e.g. Lung, Skin) CTC Measured Toxicities. | Time to local failure (local control) over 5 years follow-up after completion of therapy | Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations. |
| Muscle Function Over Time, PET, DCE-MR, T2* MR Quantitative Parameters. | Change from baseline as well as comparison to non-treated side (when available) during the first 5 years after completion of therapy. | Describe the severity and time course of radiation-induced changes in the soft tissues and adjacent organs, including muscle and subcutaneous tissues. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMatthew Krasin, MD
St. Jude Children's Research Hospital
Participant flow
Recruitment details
202 participants were enrolled between January 10, 2003 and July, 9, 2014.
Pre-assignment details
A total of 202 patients were enrolled in the study. Of 202 patients, 167 patients completed the study requirements, progression, death, and secondary malignancy, 9 patients still are in follow-up, and 26 patients were off study early due to parent or patient request, PI discretion, physician's discretion, Ineligible, and not returning to St. Jude. Completed ACT trial.
Participants by arm
| Arm | Count |
|---|---|
| Treatment Eligible patients will be accessioned at the time of irradiation and undergo a pre-radiotherapy evaluation, treatment planning, image-guided radiotherapy delivery and intra-and post-irradiation evaluations.
image-guided radiotherapy: Conformal limited image radiotherapy is radiation therapy that targets tumors with a prescribed dose of radiation which allows the surrounding normal tissues to remain basically untreated.
A total of 202 patients were enrolled in the study. Of 202 patients, 167 patients completed the study requirements, progression, death, and secondary malignancy, 9 patients still are in follow-up, and 26 patients were off study early due to parent or patient request, PI discretion, physician's discretion, Ineligible, and not returning to St. Jude. Completed ACT trial. | 202 |
| Total | 202 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Continuous | 11.84 Years STANDARD_DEVIATION 6.11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 190 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race/Ethnicity, Customized Black | 45 Participants |
| Race/Ethnicity, Customized Black and White | 2 Participants |
| Race/Ethnicity, Customized Other | 3 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants |
| Race/Ethnicity, Customized White | 151 Participants |
| Sex: Female, Male Female | 91 Participants |
| Sex: Female, Male Male | 111 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 199 |
| other Total, other adverse events | 50 / 199 |
| serious Total, serious adverse events | 9 / 199 |
Outcome results
Primary
Cumulative Incidence of Local Failures at 10 Years in Patients With Image Guided Radiation Therapy
The cumulative incidence of local failures is used to report the control of local failures in patients with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST).
Time frame: 10- years follow-up after completion of therapy
Population: Of 202 patients enrolled in the study, 199 patients were treated with radiation therapy. Three patients were off study before radiation therapy. Cumulative incidence of local failure is calculated from completion of RT to dates of local failure, distant failure (metastatic), the secondary malignancy, death, or off study (last contact) while distant failure (metastatic), the secondary malignancy, and death are considered as competing risks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Cumulative Incidence of Local Failures at 10 Years in Patients With Image Guided Radiation Therapy | 14.31 percentage of patients |
Primary
Cumulative Incidence of Local Failures at 5 Years in Patients With Image Guided Radiation Therapy
The cumulative incidence of local failures is used to report the control of local failures in patients with image guided radiation therapy as defined in this study for patients with primary musculoskeletal tumors (MST).
Time frame: 5-years follow-up after completion of therapy.
Population: Of 202 patients enrolled in the study, 199 patients were treated with radiation therapy. Three patients were off study before radiation therapy. Cumulative incidence of local failure is calculated from completion of RT to dates of local failure, distant failure (metastatic), the secondary malignancy, death, or off study (last contact) while distant failure (metastatic), the secondary malignancy, and death are considered as competing risks.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment | Cumulative Incidence of Local Failures at 5 Years in Patients With Image Guided Radiation Therapy | 13.37 percentage of patients |
Secondary
Changes in Growth Rate and Length of Bone, Bone Density, Development of Muscle (Muscle Function, e.g. Range of Motion), Occurrence of Organ Specific (e.g. Lung, Skin) CTC Measured Toxicities.
Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations.
Time frame: Time to local failure (local control) over 5 years follow-up after completion of therapy
Secondary
Changes in Growth Rate and Length of Bone, Bone Density, Development of Muscle (Muscle Function, e.g. Range of Motion), Occurrence of Organ Specific (e.g. Lung, Skin) CTC Measured Toxicities.
Investigate the dose and volume relationship for the developing physis and cortical bone using physical measures and imaging evaluations.
Time frame: Time to local failure (local control) over 10 years follow-up after completion of therapy
Secondary
Muscle Function Over Time, PET, DCE-MR, T2* MR Quantitative Parameters.
Describe the severity and time course of radiation-induced changes in the soft tissues and adjacent organs, including muscle and subcutaneous tissues.
Time frame: Change from baseline as well as comparison to non-treated side (when available) during the first 5 years after completion of therapy.