Soft Tissue Sarcoma
Conditions
Keywords
soft tissue sarcoma
Brief summary
This is a nonrandomized Phase II pilot protocol to determine the feasibility, toxicity and disease control (local control, overall and progression-free survival) using hypofractionated preoperative radiation therapy in patients with primary localized soft tissue sarcomas (STS).
Detailed description
BACKGROUND OVERVIEW: Hypofractionation has several potential advantages over conventional radiation. First, the biological equivalent dose to the tumor is higher with hypofractionation than it is with conventional radiation. In between radiation treatments there is repair of the radiation damaged cancer cells (on a cell survival curve this region of repair is referred to as the shoulder of the curve). Some cell lines are better at repair than others. Sarcoma is often referred to as a radioresistant tumor, which means that sarcoma cell lines have a larger capacity for radiation repair than do other cell lines. A treatment that can deliver a high dose in fewer fractions can potentially overcome some of this repair. There is a concept in radiation known as biologically equivalent dose (BED) which states that a higher dose per fraction results in more tumor kill than a lower dose per fraction. For example, radiation delivered to a total of 60 Gy in three 20 Gy fractions is the equivalent of 150 Gy in 2 Gy fractions. BACKGROUND RATIONALE: It is important to conduct this study because hypofractionation not only decreases treatment package time and cost of care, but it also potentially improves patient convenience and quality of life and could impact radiologic and pathologic variables in a positive way by leading to more tumor cell kill. This could potentially change the paradigm of the current management of STS of the extremity and chest-wall. HYPOTHESIS: Preoperative hypofractionated radiation therapy for localized soft tissue sarcomas (STS) will result in local control and toxicity similar to conventional fractionation with less cost, more patient convenience and decreased overall treatment time. TREATMENT: Image-guided radiation therapy is mandatory. PREOPERATIVE: (1) Either 3D conformal radiotherapy or intensity modulated radiation therapy (IMRT). (2) A prescription dose of 35 Gy in 5 fractions given every other day with at least 48 hours in between each fraction will be prescribed to cover 95% of the planning target volume. TREATMENT SCHEDULE: Treatments will have a minimum of a 48-hour interfraction interval. Treatments will be completed over 20 days maximum.
Interventions
RADIATIONHypofractionated Radiation Therapy
Treatments will have a minimum of a 48-hour interfraction interval. Treatments will be completed over 20 days maximum.
Sponsors
Medical College of Wisconsin
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age * Core needle biopsy obtained * Pathologic confirmation of primary soft tissue sarcoma of the upper or lower extremity or chest-wall. * Stage I-III Soft Tissue Sarcoma of the extremity without evidence of metastatic disease * Medically operable * No prior radiotherapy to primary site or adjacent site that results in overlapping radiation fields. * MRI obtained of the affected extremity or chest-wall * CT chest acquired to assess distant disease * Karnofsky Performance Status (KPS) 60 or above * Informed consent obtained prior to study entry
Exclusion criteria
* Patients who have metastatic disease * Pregnant women * Women of childbearing potential and male participants must practice adequate contraception. * Disease pathology other than sarcoma subtypes * Patients with a history of metastatic disease from a primary other than sarcoma * Patients who cannot undergo MRI as part of pre-treatment or treatment planning process * STS of non-extremity or chest-wall regions * Tumor size ≥ 20 cm maximal dimension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Local Disease Control Assessed by Physical Examination | 2 Years | This measure will capture the number of subjects experiencing a recurrence of the primary lesion assessed by physical examination. |
| Local Disease Control Assessed by Magnetic Resonance Imaging (MRI) | 2 years | This measure is the number of subjects experiencing a recurrence of the primary lesion as assessed by MRI. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free Survival | 2 Years | Disease-free survival will measure the time in months from initiation of radiation therapy until documented recurrence of disease. Patients who are disease-free and alive at the time of analysis will be censored at the time of their last follow-up. Patients will be assessed for disease-free survival at 2 years. |
| Overall Survival | 2 Years | Overall survival will measure the time from initiation of radiation therapy until documented death from any cause. Patients who are alive at the time of analysis will be censored at the time of their last follow-up. Patients will be assessed for overall survival at 2 years. |
| Radiologic Changes Due to Hypofractionated Radiation. | 4 weeks after radiation therapy | This measure will assess the size of enhancement due to hypofractionated radiation. |
| Treatment-related Necrosis and Fibrosis | 2 years | Number of participants who experienced treatment-related necrosis and fibrosis ≥90%. |
| Pathologic Changes Due to Hypofractionated Radiation. | 2 weeks after surgery | This measure will capture the fibrosis present in tissue specimens as a percent. |
| Musculoskeletal Tumor Rating Scale (MSTS) Score | Baseline, prior to surgery and 24 months after surgery | Toxicity will be assessed at specific times the Musculoskeletal Tumor Rating Scale. The MSTS evaluates: pain, function, emotional acceptance, hand positioning, dexterity and lifting ability, using a six-item Likert scale ranging from 0 (worst condition) to 5 (best condition). The individual scores are added for the MSTS Score, range 0 to 30. A higher score indicates better function. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Hypofractionated Radiation Therapy Radiation treatment in which the total dose of radiation is divided into large doses and treatments are given every other day. Hypofractionated radiation therapy is given over a shorter period of time (fewer days or weeks) than standard radiation therapy.
Hypofractionated Radiation Therapy: Treatments will have a minimum of a 48-hour interfraction interval. Treatments will be completed over 20 days maximum. | 35 |
| Total | 35 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
Baseline characteristics
| Characteristic | Hypofractionated Radiation Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 18 Participants |
| Age, Categorical Between 18 and 65 years | 17 Participants |
| Age, Continuous | 63.2 years STANDARD_DEVIATION 15.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 33 Participants |
| Region of Enrollment United States | 35 participants |
| Sex: Female, Male Female | 16 Participants |
| Sex: Female, Male Male | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 35 |
| other Total, other adverse events | 20 / 35 |
| serious Total, serious adverse events | 19 / 35 |
Outcome results
Primary
Local Disease Control Assessed by Magnetic Resonance Imaging (MRI)
This measure is the number of subjects experiencing a recurrence of the primary lesion as assessed by MRI.
Time frame: 2 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypofractionated Radiation Therapy | Local Disease Control Assessed by Magnetic Resonance Imaging (MRI) | 0 Participants |
Primary
Local Disease Control Assessed by Physical Examination
This measure will capture the number of subjects experiencing a recurrence of the primary lesion assessed by physical examination.
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypofractionated Radiation Therapy | Local Disease Control Assessed by Physical Examination | 0 Participants |
Secondary
Disease-free Survival
Disease-free survival will measure the time in months from initiation of radiation therapy until documented recurrence of disease. Patients who are disease-free and alive at the time of analysis will be censored at the time of their last follow-up. Patients will be assessed for disease-free survival at 2 years.
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypofractionated Radiation Therapy | Disease-free Survival | 32 Participants |
Secondary
Musculoskeletal Tumor Rating Scale (MSTS) Score
Toxicity will be assessed at specific times the Musculoskeletal Tumor Rating Scale. The MSTS evaluates: pain, function, emotional acceptance, hand positioning, dexterity and lifting ability, using a six-item Likert scale ranging from 0 (worst condition) to 5 (best condition). The individual scores are added for the MSTS Score, range 0 to 30. A higher score indicates better function.
Time frame: Baseline, prior to surgery and 24 months after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hypofractionated Radiation Therapy | Musculoskeletal Tumor Rating Scale (MSTS) Score | Baseline | 29 units on a scale | Standard Deviation 1.05 |
| Hypofractionated Radiation Therapy | Musculoskeletal Tumor Rating Scale (MSTS) Score | Prior to Surgery | 28.3 units on a scale | Standard Deviation 2.06 |
| Hypofractionated Radiation Therapy | Musculoskeletal Tumor Rating Scale (MSTS) Score | 2 years | 27.3 units on a scale | Standard Deviation 2.47 |
Secondary
Overall Survival
Overall survival will measure the time from initiation of radiation therapy until documented death from any cause. Patients who are alive at the time of analysis will be censored at the time of their last follow-up. Patients will be assessed for overall survival at 2 years.
Time frame: 2 Years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Hypofractionated Radiation Therapy | Overall Survival | 32 Participants |
Secondary
Pathologic Changes Due to Hypofractionated Radiation.
This measure will capture the fibrosis present in tissue specimens as a percent.
Time frame: 2 weeks after surgery
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Hypofractionated Radiation Therapy | Pathologic Changes Due to Hypofractionated Radiation. | Necrosis | 17.5 percentage of tumor specimen | Standard Deviation 26.4429 |
| Hypofractionated Radiation Therapy | Pathologic Changes Due to Hypofractionated Radiation. | Fibrosis | 20 percentage of tumor specimen | Standard Deviation 32.5364 |
| Hypofractionated Radiation Therapy | Pathologic Changes Due to Hypofractionated Radiation. | Viable Cells | 50 percentage of tumor specimen | Standard Deviation 31.9287 |
Secondary
Radiologic Changes Due to Hypofractionated Radiation.
This measure will assess the size of enhancement due to hypofractionated radiation.
Time frame: 4 weeks after radiation therapy
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Hypofractionated Radiation Therapy | Radiologic Changes Due to Hypofractionated Radiation. | -16.2 cubic centimeters | Standard Deviation 25 |
Secondary
Treatment-related Necrosis and Fibrosis
Number of participants who experienced treatment-related necrosis and fibrosis ≥90%.
Time frame: 2 years
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Hypofractionated Radiation Therapy | Treatment-related Necrosis and Fibrosis | Treatment-related fibrosis | 4 Participants |
| Hypofractionated Radiation Therapy | Treatment-related Necrosis and Fibrosis | Treatment-related necrosis | 4 Participants |