Trial Outcomes & Findings for Stereotactic Radiation Therapy for Pediatric Sarcomas (NCT NCT01763970)

Last Updated: 2020-08-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

14 participants

Primary outcome timeframe

6 months post-SBRT

Results posted on

2020-08-27

Participant Flow

Participant milestones

Participant milestones
Measure	Hypofractionated SBRT This is a single-arm, prospective trial to examine the efficacy and safety of SBRT (SBRT) for the treatment of bone metastases in pediatric and young adult patients. Patients with metastatic nonrhabdomyosarcoma with bone metastases were treated with SBRT to a total dose of 40 Gy in 5 fractions (8 Gy/fraction). Physicians were permitted to treat up to five distinct lesions per patient.
Overall Study STARTED	14
Overall Study COMPLETED	14
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Stereotactic Radiation Therapy for Pediatric Sarcomas

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Hypofractionated SBRT n=14 Participants 800 delivered in 5 fractions every day to total dose of 4000 SBRT: 800 delivered in 5 fractions every day to total dose of 4000
Age, Continuous	17 years n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	9 Participants n=5 Participants
Race/Ethnicity, Customized Caucasian	9 Participants n=5 Participants
Race/Ethnicity, Customized Non-Caucasian	5 Participants n=5 Participants
Region of Enrollment United States	14 Participants n=5 Participants
Lansky Play-Performance Scale (LPS) for Pediatric Functional Status LPS = 100	3 Participants n=5 Participants
Lansky Play-Performance Scale (LPS) for Pediatric Functional Status LPS = 80-90	10 Participants n=5 Participants
Lansky Play-Performance Scale (LPS) for Pediatric Functional Status LPS = 70	1 Participants n=5 Participants
Lansky Play-Performance Scale (LPS) for Pediatric Functional Status LPS < 70	0 Participants n=5 Participants
Histological type of cancer Ewing sarcoma	7 Participants n=5 Participants
Histological type of cancer Osteosarcoma	3 Participants n=5 Participants
Histological type of cancer Soft-tissue sarcoma	4 Participants n=5 Participants
Number of Lesions Treated in Each Patient	2.5 lesions n=5 Participants
Consolidation of Metastatic Disease Total	8 Participants n=5 Participants
Consolidation of Metastatic Disease Partial	6 Participants n=5 Participants
Prior systemic therapy	14 Participants n=5 Participants
Pain at baseline Yes, has pain	6 Participants n=5 Participants
Pain at baseline No pain	8 Participants n=5 Participants
Treatment Duration	7 days n=5 Participants

PRIMARY outcome

Timeframe: 6 months post-SBRT

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=37 lesions SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Lesion-specific Local Control at 6 Months Post-SBRT as Assessed by Percentage of Lesions Locally Controlled	95 percentage of lesions Interval 68.0 to 99.0	—

SECONDARY outcome

Timeframe: 6 months post-SBRT

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.

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=14 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Patient-specific Local Control at 6 Months Post-SBRT as Assessed by the Percentage of Patients Locally Controlled	89 percentage of patients Interval 43.0 to 98.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=14 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Percentage of Patients With Progression-free Survival at 6 Months Post-SBRT	50 percentage of patients Interval 23.0 to 93.0	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=14 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Percentage of Patients With Overall Survival at 6 Months Post-SBRT	100 percentage of patients	—

SECONDARY outcome

Timeframe: Baseline and one-month post-SBRT

Population: BPI forms were completed for 10 patients at baseline and one-month post-SBRT.

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.

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=10 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Change in Quality of Life (QoL) as Assessed by the Brief Pain Inventory Baseline	2 score on a scale Standard Deviation 2.4	—
Change in Quality of Life (QoL) as Assessed by the Brief Pain Inventory One month	2.1 score on a scale Standard Deviation 2.8	—

SECONDARY outcome

Timeframe: 12 months after treatment starts

To describe the toxicity of SBRT delivered to study patients measured by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=14 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Number of Participants Experiencing Toxicity of SBRT	9 Participants	—

POST_HOC outcome

Timeframe: 3 years post-SBRT

The Kaplan-Meier method was used to calculate progression-free survival (in months) stratified by consolidation status (total consolidation vs. partial consolidation) from initiation of SBRT to progression (local or distant) or death due to any cause.

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=6 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation n=8 Participants SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Progression-Free Survival by Consolidation Status	3.7 months Interval 1.4 to 6.4	9.3 months Interval 3.0 to Upper limit not reached.

POST_HOC outcome

Timeframe: 3 years post-SBRT

The Kaplan-Meier method was used to calculate overall survival (in months) stratified by consolidation status (total consolidation vs. partial consolidation) from initiation of SBRT to death due to any cause.

Outcome measures

Outcome measures
Measure	Hypofractionated SBRT n=6 Participants SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy	Total Consolidation n=8 Participants SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.
Overall Survival by Consolidation Status	12.7 months Interval 9.8 to 24.2	NA months Interval 23.3 to Median and upper limit not reached.

Adverse Events

Hypofractionated SBRT

Serious events: 2 serious events

Other events: 8 other events

Deaths: 8 deaths

Serious adverse events

Serious adverse events
Measure	Hypofractionated SBRT n=14 participants at risk 800 delivered in 5 fractions every day to total dose of 4000 SBRT: 800 delivered in 5 fractions every day to total dose of 4000
Gastrointestinal disorders Esophagitis	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Musculoskeletal and connective tissue disorders Soft tissue necrosis and fracture	7.1% 1/14 • Number of events 2 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.

Other adverse events

Other adverse events
Measure	Hypofractionated SBRT n=14 participants at risk 800 delivered in 5 fractions every day to total dose of 4000 SBRT: 800 delivered in 5 fractions every day to total dose of 4000
Skin and subcutaneous tissue disorders alopecia	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Respiratory, thoracic and mediastinal disorders nasal congestion	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Musculoskeletal and connective tissue disorders myositis	7.1% 1/14 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
General disorders Fatigue	14.3% 2/14 • Number of events 2 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Musculoskeletal and connective tissue disorders Back Pain	21.4% 3/14 • Number of events 4 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Nervous system disorders Lower Extremity Weakness	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Musculoskeletal and connective tissue disorders Wrist Pain	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Skin and subcutaneous tissue disorders Skin Hyperpigmentation	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Musculoskeletal and connective tissue disorders Compression Fracture	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.
Nervous system disorders Paresthesia of the lower extremity	7.1% 1/14 • Number of events 1 • 36 months. All of the adverse events were collected on systematic assessment except for the single patient who developed two grade 3 toxicities after treatment with SBRT. This patient developed osteonecrosis of the soft tissue of the wrist requiring curettage and grafting and subsequently fractured at the site of the graft. As such, this patient presented acutely and these toxicities were not picked up on systematic assessment.

Additional Information

Matthew Ladra,MD

SKCCC at Johns Hopkins

Phone: (202) 537-4788

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place