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Sarcoma

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Soft Tissue Sarcoma

800 cGy delivered in 5 fractions every day to total dose of 4000 cGy

SBRT

Matthew Ladra, M.D.

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.

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.

Stereotactic Radiation Therapy for Pediatric Sarcomas

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

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.

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.

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.

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.

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.

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

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

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

Hypofractionated SBRT

Age, Continuous

Sex: Female, Male

Caucasian

Non-Caucasian

Race/Ethnicity, Customized

United States

Region of Enrollment

LPS = 100

LPS = 80-90

LPS = 70

LPS < 70

The LPS for Pediatric Functional Status uses parent description of child's activity. A score of:

100 - fully active 90 - minor restrictions in strenuous physical activity 80 - active, but gets tired more quickly 70 - greater restriction of play and less time spent in play activity 60 - up and around, but active play minimal 50 - lying around much of the day, but gets dressed 40 - mainly in bed; participates in quiet activities 30 - bedbound; needing assistance even for quiet play 20 - sleeping often; play entirely limited to very passive activities 10 - doesn't play 0 - unresponsive

Lansky Play-Performance Scale (LPS) for Pediatric Functional Status

Ewing sarcoma

Osteosarcoma

Soft-tissue sarcoma

Histological type of cancer

Number of Lesions Treated in Each Patient

Total

Partial

If a patient had all known sites of metastatic disease treated they were coded as total consolidation. If not all sites of metastatic disease were treated, they were coded as partial consolidation.

Consolidation of Metastatic Disease

Number of participants who received prior systemic therapy

Prior systemic therapy

Yes, has pain

No pain

Pain at baseline

Treatment Duration

Matthew Ladra,MD

SBRT: 800 centigray (cGy) delivered in 5 fractions every day to total dose of 4000 cGy

Lesion-specific Local Control at 6 Months Post-SBRT as Assessed by Percentage of Lesions Locally Controlled

SBRT: 800 cGy delivered in 5 fractions every day to total dose of 4000 cGy

Patient-specific Local Control at 6 Months Post-SBRT as Assessed by the Percentage of Patients Locally Controlled

Percentage of Patients With Progression-free Survival at 6 Months Post-SBRT

Percentage of Patients With Overall Survival at 6 Months Post-SBRT

Baseline

One month

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

Change in Quality of Life (QoL) as Assessed by the Brief Pain Inventory

Number of Participants Experiencing Toxicity of 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.

SBRT: 800 cGy delivered in 5 fractions every day to total dose of 4000 cGy. Not all sites of metastatic disease were treated (partial consolidation).

Partial Consolidation

SBRT: 800 cGy delivered in 5 fractions to a total dose of 4000 cGy. All known sites of metastatic disease were treated.

Total Consolidation

Progression-Free Survival by Consolidation Status

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.

Overall Survival by Consolidation Status

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.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Stereotactic Radiation Therapy for Pediatric Sarcomas	NCT01763970	Sarcoma Metastatic Dise... Bony Sites	SBRT	4 Years - 40 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Stereotactic Radiation Therapy for Pediatric Sarcomas	NCT01763970	Sarcoma Metastatic Dise... Bony Sites	SBRT	4 Years - 40 Years	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Spots Global Cancer Trial Database for bony sites

Every month we try and update this database with for bony sites cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bony sites

Every month we try and update this database with for bony sites cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bony sites cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.