Adult Rhabdomyosarcoma, Lung Metastases, Metastatic Ewing Sarcoma, Previously Treated Childhood Rhabdomyosarcoma, Recurrent Adult Soft Tissue Sarcoma, Recurrent Childhood Rhabdomyosarcoma, Recurrent Wilms Tumor and Other Childhood Kidney Tumors, Stage IV Adult Soft Tissue Sarcoma, Stage IV Wilms Tumor, Stage V Wilms Tumor, Unspecified Adult Solid Tumor, Protocol Specific, Unspecified Childhood Solid Tumor, Protocol Specific
Conditions
Brief summary
This pilot clinical trial studies intensity-modulated radiation therapy (IMRT) in treating younger patients with lung metastases. Specialized radiation therapy that delivers a high dose of radiation directly to the tumor may kill more tumor cells and cause less damage to normal tissue.
Detailed description
OBJECTIVES: I. To demonstrate the feasibility of delivering cardiac-sparing IMRT in a multi-institutional setting with central quality control for children and young adults with metastatic tumors in the lungs. II. To prospectively determine the dosimetric advantages of whole lung IMRT treatment over standard whole lung irradiation by comparing treatment plans and different organ dose-volume histograms such as lungs, heart, thyroid gland, liver etc. in all patients enrolled in this study. III. To determine the short-term efficacy (lung-metastases free survival) and acute tolerance of whole lung IMRT at a minimum period of six months after IMRT. OUTLINE: Patients undergo cardiac-sparing whole lung IMRT. After completion of study treatment, patients are followed up for 1-5 years.
Interventions
RADIATIONintensity-modulated radiation therapy
Undergo cardiac-sparing whole lung IMRT
Sponsors
Northwestern University
National Cancer Institute (NCI)
Ann & Robert H Lurie Children's Hospital of Chicago
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Years to 29 Years
Healthy volunteers
No
Inclusion criteria
* Patients may have a Wilms tumor, Ewing Sarcoma, Rhabdomyosarcoma or any other metastatic pediatric malignancy; patients may have a single or multiple pulmonary metastases at the time of diagnosis or at the time of recurrence; a pulmonary metastasis may be defined as one pulmonary nodule \>= 1 cm or more than one pulmonary nodules \>= 0.5 cm; a biopsy of the nodules may be considered in case of doubt * The Karnofsky performance status must be \>= 50 for patients \> 16 years of age and the Lansky performance status must be \>= 50 for patients =\< 16 years of age * Patients must not have received prior radiation therapy to any part of the thorax * Adequate cardiac function defined as: * Shortening fraction of \>= 27% by echocardiogram, or * Ejection fraction of \>= 50% by radionuclide angiogram * Female patients of childbearing age must have a negative pregnancy test * Female patients who are lactating must agree to stop breast-feeding * Sexually active patients of childbearing potential must agree to use effective contraception
Exclusion criteria
* Patients enrolled on Children's Oncology Group protocols cannot be treated with whole lung IMRT on this study * Patients who have a prior history of radiation therapy to the thorax or adjacent regions cannot be entered on this protocol * Patient with Hodgkin's Lymphoma are not eligible for this study * Patients with mediastinal masses or other pulmonary masses requiring additional mediastinal or lung irradiation beyond the whole lung irradiation (WLI) doses stated in this protocol are ineligible for this study * Patients who may require concurrent or sequential irradiation to sites beyond the chest such as the neck, flank, abdomen or liver are eligible for this study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Feasibility of Delivering Cardiac-sparing IMRT With Central Quality Control in 20 Subjects | All IMRT treatment plans were centrally reviewed within 1-2 days of receipt of the radiation therapy plan. The feasibility was determined as 'feasible' if deemed in accordance with protocol guidelines after central QARC review within 1-2 days of receipt. | Feasibility is defined as an enrolled patient receiving the IMRT treatment as stipulated in the protocol. Feasibility of delivering whole lung IMRT will be demonstrated by obtaining central (Quality Assurance Review Center 'QARC') quality control approval of enrolled patient treatment plans according to the protocol guidelines for the 20 subjects enrolled onto the study. If an enrolled patient did not receive the IMRT treatment as stipulated in the protocol this subject then the treatment will be considered not feasible in this patient. |
| Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | From date of enrollment until the date of first documented progression, relapse or date of death from any cause up to an average of 3 years. | Serial CT scans of the chest were examined to determine lung-metastasis free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Radiation Dose to Organ Volumes | This outcome is measured from central review of radiation plans within 1-2 days of receipt. | The IMRT and standard anteroposterior (AP-PA) treatment plans were reviewed and compared for target coverage and organ dose-volume histograms. The mean percentage volume of the organ or organ sub-region receiving a percentage of the dose was estimated from the computerized treatment plans for these two techniques were estimated and compared statistically |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment (IMRT) Patients undergo cardiac-sparing whole lung intensity-modulated radiation therapy (IMRT).
intensity-modulated radiation therapy: Undergo cardiac-sparing whole lung IMRT | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Treatment (IMRT) |
|---|---|
| Age, Continuous | 13 years |
| Region of Enrollment United States | 20 Participants |
| Sex: Female, Male Female | 9 Participants |
| Sex: Female, Male Male | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 2 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 2 / 20 |
Outcome results
Primary
Feasibility of Delivering Cardiac-sparing IMRT With Central Quality Control in 20 Subjects
Feasibility is defined as an enrolled patient receiving the IMRT treatment as stipulated in the protocol. Feasibility of delivering whole lung IMRT will be demonstrated by obtaining central (Quality Assurance Review Center 'QARC') quality control approval of enrolled patient treatment plans according to the protocol guidelines for the 20 subjects enrolled onto the study. If an enrolled patient did not receive the IMRT treatment as stipulated in the protocol this subject then the treatment will be considered not feasible in this patient.
Time frame: All IMRT treatment plans were centrally reviewed within 1-2 days of receipt of the radiation therapy plan. The feasibility was determined as 'feasible' if deemed in accordance with protocol guidelines after central QARC review within 1-2 days of receipt.
Population: 14 patients had pediatric sarcomas; 5 had Wilms tumor; 1 had hepatoblastoma. 15/20 received RT to primary site. 15 had CS-IMRT as part of primary therapy vs 5 had CS-IMRT at relapse/progressive disease. At time of CS-IMRT, 18/20 patients' lung tumors were in remission/stable \& 2 had progressive disease.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (IMRT) | Feasibility of Delivering Cardiac-sparing IMRT With Central Quality Control in 20 Subjects | 20 Participants |
Primary
Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease)
Serial CT scans of the chest were examined to determine lung-metastasis free survival
Time frame: From date of enrollment until the date of first documented progression, relapse or date of death from any cause up to an average of 3 years.
Population: Overall survival and incidence rates of additional relevant clinical data
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | 2yr overall survival | 18 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | Pulmonary relapse - after primary therapy | 4 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | Pulmonary relapse - after relapse/progression | 4 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | Deceased from progressive disease | 2 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | 3yr overall survival | 18 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | 2yr lung-metastasis progression free survival | 13 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | 3yr lung-metastasis progression free survival | 10 Participants |
| Treatment (IMRT) | Short-term Efficacy (Lung-metastases Free Survival, Overall Survival, Pulmonary Relapse, Deceased From Progressive Disease) | Pulmonary relapse | 8 Participants |
Secondary
Mean Percentage Radiation Dose to Organ Volumes
The IMRT and standard anteroposterior (AP-PA) treatment plans were reviewed and compared for target coverage and organ dose-volume histograms. The mean percentage volume of the organ or organ sub-region receiving a percentage of the dose was estimated from the computerized treatment plans for these two techniques were estimated and compared statistically
Time frame: This outcome is measured from central review of radiation plans within 1-2 days of receipt.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Ventricle - V50 (%) for IMRT | 95 Mean % radiation dose to % organ volume | Standard Deviation 7.8 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Heart - V50 (%) for IMRT | 96 Mean % radiation dose to % organ volume | Standard Deviation 5.4 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Heart - V50 (%) for AP- PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 0.8 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Heart - V83 (%) for IMRT | 65 Mean % radiation dose to % organ volume | Standard Deviation 12.1 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Heart - V83 (%) for AP-PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 2.2 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Heart - V95 (%) for IMRT | 39 Mean % radiation dose to % organ volume | Standard Deviation 15.5 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Heart- V95 (%) for AP-PA | 97 Mean % radiation dose to % organ volume | Standard Deviation 6.7 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Ventricle - V50 (%) for AP-PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 0 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Ventricle - V95 (%) for IMRT | 33 Mean % radiation dose to % organ volume | Standard Deviation 15.9 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Ventricle - V95 (%) for AP-PA | 99 Mean % radiation dose to % organ volume | Standard Deviation 2.7 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Ventricle - V50 (%) for IMRT | 91 Mean % radiation dose to % organ volume | Standard Deviation 9.8 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Ventricle - V50 (%) for AP-PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 1.6 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Ventricle - V83 (%) for IMRT | 42 Mean % radiation dose to % organ volume | Standard Deviation 12.7 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Ventricle - V83 (%) for AP-PA | 99 Mean % radiation dose to % organ volume | Standard Deviation 4 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Ventricle - V95 (%) for IMRT | 18 Mean % radiation dose to % organ volume | Standard Deviation 8.9 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Ventricle - V95 (%) for AP-PA | 97 Mean % radiation dose to % organ volume | Standard Deviation 8.2 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Atrium - V50 (%) for IMRT | 99 Mean % radiation dose to % organ volume | Standard Deviation 0.4 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Atrium - V50 (%) for AP-PA | 99 Mean % radiation dose to % organ volume | Standard Deviation 0.7 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Atrium - V95 (%) for IMRT | 57 Mean % radiation dose to % organ volume | Standard Deviation 22.5 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Atrium - V95 (%) for AP-PA | 97 Mean % radiation dose to % organ volume | Standard Deviation 11.1 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Atrium V50 (%) for IMRT | 99 Mean % radiation dose to % organ volume | Standard Deviation 0.4 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Atrium V50 (%) for AP-PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 0.2 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Atrium - V95 (%) for IMRT | 55 Mean % radiation dose to % organ volume | Standard Deviation 22.3 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Atrium - V95 (%) for AP-PA | 94 Mean % radiation dose to % organ volume | Standard Deviation 15.4 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Coronary Artery - V95 (%) for IMRT | 100 Mean % radiation dose to % organ volume | Standard Deviation 0 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Right Coronary Artery - V95 (%) for AP-PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 0 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Coronary Artery - V95 (%) for IMRT | 88 Mean % radiation dose to % organ volume | Standard Deviation 9.9 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Left Coronary Artery - V95 (%) for AP-PA | 99 Mean % radiation dose to % organ volume | Standard Deviation 1.3 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Myocardium - V50 (%) for IMRT | 94 Mean % radiation dose to % organ volume | Standard Deviation 8 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Myocardium - V50 (%) for AP-PA | 100 Mean % radiation dose to % organ volume | Standard Deviation 0 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Myocardium - V95 (%) for IMRT | 69 Mean % radiation dose to % organ volume | Standard Deviation 7.56 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Myocardium - V95 (%) for AP-PA | 99 Mean % radiation dose to % organ volume | Standard Deviation 0.88 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Thyroid - V50 (%) for IMRT | 44 Mean % radiation dose to % organ volume | Standard Deviation 32.5 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Thyroid - V50 (%) for AP-PA | 33 Mean % radiation dose to % organ volume | Standard Deviation 31.3 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Kidneys - V50 (%) for IMRT | 5 Mean % radiation dose to % organ volume | Standard Deviation 7.6 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Kidneys - V50 (%) for AP-PA | 6 Mean % radiation dose to % organ volume | Standard Deviation 6.8 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Stomach - V50 (%) for IMRT | 62 Mean % radiation dose to % organ volume | Standard Deviation 21.7 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Stomach - V50 (%) for AP-PA | 62 Mean % radiation dose to % organ volume | Standard Deviation 24.5 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Liver - V50 (%) for IMRT | 55 Mean % radiation dose to % organ volume | Standard Deviation 11.4 |
| Treatment (IMRT) | Mean Percentage Radiation Dose to Organ Volumes | Liver - V50 (%) for AP-PA | 54 Mean % radiation dose to % organ volume | Standard Deviation 11.4 |
Comparison: Feasibility will be defined as an enrolled patient receiving the IMRT treatment as planned. It is expected that the treatment will be feasible in at least 90% of patients. If the treatment is feasible in 16 or more out of 20 patients, then the treatment will be declared feasible. If the true feasibility rate is 90%, then there is a 4.3% chance that 15 or fewer feasible patients will be observed.p-value: <0.0125Bonferroni corrected at p<0.0125