Brain Cancer, Cancer of Brain and Nervous System, Metastatic Malignant Neoplasm to Brain, Neoplasm Metastasis
Conditions
Brief summary
The maximum tolerated dose of 3-session (ie, treatment) stereotactic radiosurgery (SRS) to treat brain metastases greater than 4.2 cm³ in size will be determined. This study investigates if increasing radiation dose improves outcome for patients without greater toxicity (side effects).
Detailed description
Brain metastases are the most common intracranial tumors and occur in approximately 25% of patients with cancer. In the US, approximately 170,000 cancer patients a year are diagnosed with brain metastases. The prognosis of patients with brain metastases is variable and depends on several factors, including performance status, age, control of the primary tumor, and extent of extracranial disease. Historically, patients with brain metastases who receive supportive care only have median survival of 1 to 2 months. However, a subgroup of patients with favorable prognosis who undergo treatment can enjoy an extended life expectancy with median survival of 10 to 16 months. Treatment options for brain metastases include medical management, surgery, and radiation therapy (radiotherapy). Both surgery and radiotherapy have an important role in management of brain metastases, and an optimized treatment plan may include both. It is well-established that surgery followed by conventional whole brain radiation (WBRT) decreases local recurrence and improves median survival compared to WBRT alone. Conventional WBRT is administered as radiotherapy to the whole cranium delivered in 10 to 20 daily treatments. For this study, radiotherapy will be delivered using stereotactic radiosurgery (SRS) to treat individual metastases. SRS has the advantage of sparing normal brain tissue. In SRS, high energy radiation is precisely directed at the target lesion. Due to the steep fall-off of the radiation dose away from the target, the advantage of relative sparing of the normal brain may be realized. The present study is based on a rationale of treating brain metastases with surgical resection followed by adjuvant SRS to the resection cavity, while deferring conventional WBRT for salvage therapy. WBRT is associated with a short-term decline in quality of life and long-term deficits in neurocognitive function (late effects). Late toxicity of WBRT, such as memory impairment and dementia, is usually irreversible and is likely due to demyelination, vascular damage, and necrosis. Following WBRT, the actuarial rate of neurocognitive toxicity at 2 years can be up to 49%. Recipients of WBRT may demonstrate a \> 2 standard deviation decline in their performance at 6 months. Compared to SRS alone, WBRT was reported to be associated with a marked decline in learning and memory function at 4 months (49% vs 23%, in favor of SRS). To minimize the potential late effects of WBRT, investigators have explored the use of SRS alone, deferring the use of WBRT for salvage treatment if needed. Both retrospective analyses and a prospective randomized trial reported no apparent survival benefit to combining WBRT with SRS compared to SRS alone Primary Objectives: Determine the maximum tolerated dose (MTD) of stereotactic radiosurgery (SRS). Secondary Objectives: 1. Determine the local control rate as assessed on MRI and clinical exam. 2. Determine short- and long-term adverse effects. 3. Determine the distant intra-cranial control rate. 4. Determine the overall survival rate. 5. Assess the patient's health related quality of life. Treatment Group assignment will be by SRS dose level. SRS will be administered as 3 fractions. Radiation dose is administered as Greys (or Grays; abbreviated Gy), a unit by which radiation is measured. Treatment Groups are as follows: Group 1 = 24 Gy (administered as 8 Gy x 3) Group 2 = 7 Gy (9 Gy x 3); Group 3 = 30 Gy (10 Gy x 3); Group 4 = 33 Gy (11 Gy x 3). Within each Treatment Group, analysis may be stratified by tumor size and suitability for surgical resection, as below. For those participants eligible for surgical resection, the procedure will be conducted in advance of the SRS treatment. * Strata A will be those with tumors 4.2 to 14.1 cm³, and suitable for resection. * Strata B will be those with tumors 4.2 to 14.1 cm³, but not suitable for resection. * Strata C will be those with tumors 14.2 to 33.5 cm³, and suitable for resection. * Strata D will be those with tumors 14.2 to 33.5 cm³, but not suitable for resection.
Interventions
RADIATIONFractionated Stereotactic Radiosurgery (SRS)
Standard of care
PROCEDURESurgical resection
Standard of care
Sponsors
Stanford University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years and older * Pathologically-proven solid tumor malignancy * 1 to 4 brain metastases, one of which is 4.2 to 33.5 cm³. * Prior surgery or SRS is allowed as long as the target metastatic lesion in this study has not previously been treated with SRS. * Prior cytotoxic systemic therapy must be completed ≥ 5 days prior to radiosurgery. No concurrent cytotoxic systemic therapy along with SRS. Cytotoxic systemic therapy to start ≥ 5 days after the completion of SRS. * Life expectancy of ≥ 12 weeks. * Ability to understand and the willingness to sign a written informed consent.
Exclusion criteria
* Previously treated with whole brain irradiation * Target metastatic lesion previously been treated with SRS. * \> 4 total brain metastases at the time of initial evaluation. * Pregnant * Unable to give informed consent.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | 60 days | The maximum-tolerated Dose (MTD) of stereotactic radiosurgery (SRS) was assessed based on the number of dose-limiting toxicities (DLTs). DLT was defined as any treatment-related grade 3, 4, or 5 central nervous system (CNS) radiation morbidity observed within 30 days of radiosurgery. CNS radiation morbidity was further defined as. * 5 = Death * 4 = Serious neurologic impairment such as paralysis, coma, or seizures \> 3/week * 3 = Neurologic findings requiring hospitalization * 2 = Neurologic findings present sufficient to require attendant care * 1 = Fully functional status (ie, able to work) with minor neurologic findings; no medication needed * 0 = No Change The outcome is expressed as number of DLTs experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion. Per protocol, the MTD of SRS was defined as either the dose level below that at which 4+ DLTs were experienced by 12 subjects, or the maximum dose administered without MTD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant Intra-cranial Disease Control | 12 months | Distant treatment failure (failure to achieve or maintain disease control) is defined as the radiographic appearance of a new or enhancing lesion more than 5 mm from the radiosurgical target volume. The outcome is expressed as the number of participants who have distant treatment failure after radiotherapy dose cohort and tumor size, a number without dispersion. |
| Adverse Effects Within 30 Days | 30 days | Short-term adverse effects are defined as any adverse event related to the stereotactic radiosurgery (SRS), and occurring within 30 days of SRS. The outcome is expressed as the number of events experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion. |
| Adverse Effects More Than 30 Days up to 1 Year | after 30 days and up to 1 year | Long-term adverse effects are defined as any adverse event related to the stereotactic radiosurgery (SRS), and occurring more 30 days but within 12 months of SRS. The outcome is expressed as the number of events experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion. |
| Local Disease Control | 12 months | Local disease control (treatment response) was assessed on the basis of tumor size before and 12 months after treatment. Treatment response was based on the following criteria. Tumor area is determined as the product of 2 measurements of lesion diameter. * Complete response (CR): The tumor is no longer seen within the radiosurgical target volume * Partial response (PR): Decrease of \> 50% in tumor area * Minor response (MR): Decrease of \< 50% in tumor area * Stable disease (SD): The scan shows no change. * Progression (P): A \> 25% increase in tumor area, or any new lesion within the radiosurgical target volume. Local control is defined as as any treatment response other than progression. The outcome is as the number of participants that did not progress, by radiotherapy dose cohort and tumor size, a number without dispersion. |
| Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | 6 months | Health-related quality of life (HR-QoL), was assessed based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients (QLQ-C30) survey, a survey of 28 questions with the following responses / numerical values. 1. Not at all 2. A Little 3. Quite a Bit 4. Very Much Response range is 28 to 112, normalized to a 100 point scale. Lower values indicate little effect of disease, and higher values indicate greater effect. The outcome is expressed as the median value with full range, by radiotherapy dose cohort and tumor size. |
| Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | 6 months | Health-related quality of life (HR-QoL), was assessed based on the European Organisation for Research and Treatment of Cancer (EORTC) Brain Cancer Module (QLQ-BN20), a survey of 20 questions with the following responses / numerical values. 1. Not at all 2. A Little 3. Quite a Bit 4. Very Much Response range is 20 to 80, normalized to a 0 to 100 scale. Lower values indicate little effect of disease, and higher values indicate greater effect. The outcome is expressed as the median value with full range, by radiotherapy dose cohort and tumor size. |
| Overall Survival (OS) | 3 years | Overall survival (OS) is assessed as remaining alive 3 years after stereotactic radiosurgery (SRS) therapy. The outcome is expressed as the number of participants alive 3 years after SRS, by radiotherapy dose cohort and tumor size, a number without dispersion. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 - 24 Grey SRS 24 Grey administered as 8 Gy x 3 fractions
Fractionated Stereotactic Radiosurgery (SRS): Standard of care
Surgical resection: Standard of care | 20 |
| Arm 2 - 27 Grey SRS 27 Grey administered as 9 Gy x 3 fractions
Fractionated Stereotactic Radiosurgery (SRS): Standard of care
Surgical resection: Standard of care | 12 |
| Arm 3 - 30 Grey SRS 30 Grey administered as 10 Gy x 3 fractions
Fractionated Stereotactic Radiosurgery (SRS): Standard of care
Surgical resection: Standard of care | 12 |
| Arm 4 - 33 Grey SRS 33 Grey administered as 11 Gy x 3 fractions
Fractionated Stereotactic Radiosurgery (SRS): Standard of care
Surgical resection: Standard of care | 12 |
| Total | 56 |
Baseline characteristics
| Characteristic | Arm 1 - 24 Grey SRS | Arm 2 - 27 Grey SRS | Arm 3 - 30 Grey SRS | Arm 4 - 33 Grey SRS | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 7 Participants | 5 Participants | 5 Participants | 21 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 5 Participants | 7 Participants | 7 Participants | 35 Participants |
| Age, Continuous | 59.8 years STANDARD_DEVIATION 11 | 67.2 years STANDARD_DEVIATION 12 | 58.9 years STANDARD_DEVIATION 12.2 | 59.2 years STANDARD_DEVIATION 12.1 | 61.1 years STANDARD_DEVIATION 11.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants | 6 Participants | 10 Participants | 10 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 7 Participants | 0 Participants | 1 Participants | 14 Participants |
| Race (NIH/OMB) White | 13 Participants | 5 Participants | 11 Participants | 11 Participants | 40 Participants |
| Region of Enrollment United States | 20 participants | 12 participants | 12 participants | 12 participants | 56 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 5 Participants | 6 Participants | 24 Participants |
| Sex: Female, Male Male | 12 Participants | 7 Participants | 7 Participants | 6 Participants | 32 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 10 / 20 | 6 / 12 | 5 / 12 | 5 / 12 |
| other Total, other adverse events | 20 / 20 | 12 / 12 | 12 / 12 | 12 / 12 |
| serious Total, serious adverse events | 13 / 20 | 6 / 12 | 12 / 12 | 3 / 12 |
Outcome results
Primary
Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD)
The maximum-tolerated Dose (MTD) of stereotactic radiosurgery (SRS) was assessed based on the number of dose-limiting toxicities (DLTs). DLT was defined as any treatment-related grade 3, 4, or 5 central nervous system (CNS) radiation morbidity observed within 30 days of radiosurgery. CNS radiation morbidity was further defined as. * 5 = Death * 4 = Serious neurologic impairment such as paralysis, coma, or seizures \> 3/week * 3 = Neurologic findings requiring hospitalization * 2 = Neurologic findings present sufficient to require attendant care * 1 = Fully functional status (ie, able to work) with minor neurologic findings; no medication needed * 0 = No Change The outcome is expressed as number of DLTs experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion. Per protocol, the MTD of SRS was defined as either the dose level below that at which 4+ DLTs were experienced by 12 subjects, or the maximum dose administered without MTD.
Time frame: 60 days
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata D: Large tumor, not resected | 0 Dose-limited toxicity (DLT) events |
| Arm 1 - 24 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata B: Small tumor, not resected | 0 Dose-limited toxicity (DLT) events |
| Arm 1 - 24 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata C: Large tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 1 - 24 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata A: Small tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 2 - 27 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata C: Large tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 2 - 27 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata A: Small tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 3 - 30 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata C: Large tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 3 - 30 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata A: Small tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 4 - 33 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata C: Large tumor, resected | 0 Dose-limited toxicity (DLT) events |
| Arm 4 - 33 Grey SRS | Stereotactic Radiosurgery (SRS) Maximum-tolerated Dose (MTD) | Strata A: Small tumor, resected | 0 Dose-limited toxicity (DLT) events |
Secondary
Adverse Effects More Than 30 Days up to 1 Year
Long-term adverse effects are defined as any adverse event related to the stereotactic radiosurgery (SRS), and occurring more 30 days but within 12 months of SRS. The outcome is expressed as the number of events experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion.
Time frame: after 30 days and up to 1 year
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS). Only participants surviving more than 30 days are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata A: Small tumor, resected | 6 adverse events |
| Arm 1 - 24 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata B: Small tumor, not resected | 1 adverse events |
| Arm 1 - 24 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata C: Large tumor, resected | 3 adverse events |
| Arm 2 - 27 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata C: Large tumor, resected | 4 adverse events |
| Arm 2 - 27 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata A: Small tumor, resected | 1 adverse events |
| Arm 3 - 30 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata C: Large tumor, resected | 6 adverse events |
| Arm 3 - 30 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata A: Small tumor, resected | 3 adverse events |
| Arm 4 - 33 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata A: Small tumor, resected | 2 adverse events |
| Arm 4 - 33 Grey SRS | Adverse Effects More Than 30 Days up to 1 Year | Strata C: Large tumor, resected | 5 adverse events |
Secondary
Adverse Effects Within 30 Days
Short-term adverse effects are defined as any adverse event related to the stereotactic radiosurgery (SRS), and occurring within 30 days of SRS. The outcome is expressed as the number of events experienced by participants, by radiotherapy dose cohort and tumor size, a number without dispersion.
Time frame: 30 days
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Adverse Effects Within 30 Days | Strata D: Large tumor, not resected | 1 adverse events |
| Arm 1 - 24 Grey SRS | Adverse Effects Within 30 Days | Strata B: Small tumor, not resected | 3 adverse events |
| Arm 1 - 24 Grey SRS | Adverse Effects Within 30 Days | Strata C: Large tumor, resected | 4 adverse events |
| Arm 1 - 24 Grey SRS | Adverse Effects Within 30 Days | Strata A: Small tumor, resected | 3 adverse events |
| Arm 2 - 27 Grey SRS | Adverse Effects Within 30 Days | Strata C: Large tumor, resected | 2 adverse events |
| Arm 2 - 27 Grey SRS | Adverse Effects Within 30 Days | Strata A: Small tumor, resected | 4 adverse events |
| Arm 3 - 30 Grey SRS | Adverse Effects Within 30 Days | Strata C: Large tumor, resected | 2 adverse events |
| Arm 3 - 30 Grey SRS | Adverse Effects Within 30 Days | Strata A: Small tumor, resected | 4 adverse events |
| Arm 4 - 33 Grey SRS | Adverse Effects Within 30 Days | Strata C: Large tumor, resected | 3 adverse events |
| Arm 4 - 33 Grey SRS | Adverse Effects Within 30 Days | Strata A: Small tumor, resected | 2 adverse events |
Secondary
Distant Intra-cranial Disease Control
Distant treatment failure (failure to achieve or maintain disease control) is defined as the radiographic appearance of a new or enhancing lesion more than 5 mm from the radiosurgical target volume. The outcome is expressed as the number of participants who have distant treatment failure after radiotherapy dose cohort and tumor size, a number without dispersion.
Time frame: 12 months
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS). Only participants with 12-month disease status data are included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Distant Intra-cranial Disease Control | Strata A: Small tumor, resected | 4 participants |
| Arm 1 - 24 Grey SRS | Distant Intra-cranial Disease Control | Strata B: Small tumor, not resected | 2 participants |
| Arm 1 - 24 Grey SRS | Distant Intra-cranial Disease Control | Strata C: Large tumor, resected | 3 participants |
| Arm 2 - 27 Grey SRS | Distant Intra-cranial Disease Control | Strata C: Large tumor, resected | 3 participants |
| Arm 2 - 27 Grey SRS | Distant Intra-cranial Disease Control | Strata A: Small tumor, resected | 3 participants |
| Arm 3 - 30 Grey SRS | Distant Intra-cranial Disease Control | Strata C: Large tumor, resected | 3 participants |
| Arm 3 - 30 Grey SRS | Distant Intra-cranial Disease Control | Strata A: Small tumor, resected | 2 participants |
| Arm 4 - 33 Grey SRS | Distant Intra-cranial Disease Control | Strata A: Small tumor, resected | 2 participants |
| Arm 4 - 33 Grey SRS | Distant Intra-cranial Disease Control | Strata C: Large tumor, resected | 3 participants |
Secondary
Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20
Health-related quality of life (HR-QoL), was assessed based on the European Organisation for Research and Treatment of Cancer (EORTC) Brain Cancer Module (QLQ-BN20), a survey of 20 questions with the following responses / numerical values. 1. Not at all 2. A Little 3. Quite a Bit 4. Very Much Response range is 20 to 80, normalized to a 0 to 100 scale. Lower values indicate little effect of disease, and higher values indicate greater effect. The outcome is expressed as the median value with full range, by radiotherapy dose cohort and tumor size.
Time frame: 6 months
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS). Only participants with 6-month European Organisation for Research and Treatment of Cancer (EORTC) Brain Cancer Module (QLQ-BN20) health-related quality of life (HR-QoL) data are included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata A: Small tumor, resected | 0 score on a scale |
| Arm 1 - 24 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata B: Small tumor, not resected | 0 score on a scale |
| Arm 1 - 24 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata C: Large tumor, resected | 12.5 score on a scale |
| Arm 2 - 27 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata C: Large tumor, resected | 33.3 score on a scale |
| Arm 2 - 27 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata A: Small tumor, resected | 16.7 score on a scale |
| Arm 3 - 30 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata C: Large tumor, resected | 8.3 score on a scale |
| Arm 3 - 30 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata A: Small tumor, resected | 16.5 score on a scale |
| Arm 4 - 33 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata A: Small tumor, resected | 16.7 score on a scale |
| Arm 4 - 33 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC Brain Cancer Module QLQ-BN20 | Strata C: Large tumor, resected | 8.3 score on a scale |
Secondary
Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30
Health-related quality of life (HR-QoL), was assessed based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients (QLQ-C30) survey, a survey of 28 questions with the following responses / numerical values. 1. Not at all 2. A Little 3. Quite a Bit 4. Very Much Response range is 28 to 112, normalized to a 100 point scale. Lower values indicate little effect of disease, and higher values indicate greater effect. The outcome is expressed as the median value with full range, by radiotherapy dose cohort and tumor size.
Time frame: 6 months
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS). Only participants providing 6-month European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life of Cancer Patients (QLQ-C30) health-related quality of life (HR-QoL) data are included.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata A: Small tumor, resected | 100 score on a scale |
| Arm 1 - 24 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata B: Small tumor, not resected | 75 score on a scale |
| Arm 1 - 24 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata C: Large tumor, resected | 87.5 score on a scale |
| Arm 2 - 27 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata C: Large tumor, resected | 75 score on a scale |
| Arm 2 - 27 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata A: Small tumor, resected | 83.3 score on a scale |
| Arm 3 - 30 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata C: Large tumor, resected | 83.3 score on a scale |
| Arm 3 - 30 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata A: Small tumor, resected | 75 score on a scale |
| Arm 4 - 33 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata A: Small tumor, resected | 50 score on a scale |
| Arm 4 - 33 Grey SRS | Health-related Quality of Life (HR-QoL), as Measured by EORTC QLQ-C30 | Strata C: Large tumor, resected | 83.3 score on a scale |
Secondary
Local Disease Control
Local disease control (treatment response) was assessed on the basis of tumor size before and 12 months after treatment. Treatment response was based on the following criteria. Tumor area is determined as the product of 2 measurements of lesion diameter. * Complete response (CR): The tumor is no longer seen within the radiosurgical target volume * Partial response (PR): Decrease of \> 50% in tumor area * Minor response (MR): Decrease of \< 50% in tumor area * Stable disease (SD): The scan shows no change. * Progression (P): A \> 25% increase in tumor area, or any new lesion within the radiosurgical target volume. Local control is defined as as any treatment response other than progression. The outcome is as the number of participants that did not progress, by radiotherapy dose cohort and tumor size, a number without dispersion.
Time frame: 12 months
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS). Only participants with 12-month treatment response data are included.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Local Disease Control | Strata A: Small tumor, resected | 4 Participants |
| Arm 1 - 24 Grey SRS | Local Disease Control | Strata B: Small tumor, not resected | 0 Participants |
| Arm 1 - 24 Grey SRS | Local Disease Control | Strata C: Large tumor, resected | 5 Participants |
| Arm 2 - 27 Grey SRS | Local Disease Control | Strata C: Large tumor, resected | 4 Participants |
| Arm 2 - 27 Grey SRS | Local Disease Control | Strata A: Small tumor, resected | 6 Participants |
| Arm 3 - 30 Grey SRS | Local Disease Control | Strata C: Large tumor, resected | 6 Participants |
| Arm 3 - 30 Grey SRS | Local Disease Control | Strata A: Small tumor, resected | 5 Participants |
| Arm 4 - 33 Grey SRS | Local Disease Control | Strata A: Small tumor, resected | 6 Participants |
| Arm 4 - 33 Grey SRS | Local Disease Control | Strata C: Large tumor, resected | 4 Participants |
Secondary
Overall Survival (OS)
Overall survival (OS) is assessed as remaining alive 3 years after stereotactic radiosurgery (SRS) therapy. The outcome is expressed as the number of participants alive 3 years after SRS, by radiotherapy dose cohort and tumor size, a number without dispersion.
Time frame: 3 years
Population: There were few participants who did not receive tumor resection, and these were restricted to Arm 1 (24 Grey SRS).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm 1 - 24 Grey SRS | Overall Survival (OS) | Strata D: Large tumor, not resected | 0 Participants |
| Arm 1 - 24 Grey SRS | Overall Survival (OS) | Strata B: Small tumor, not resected | 2 Participants |
| Arm 1 - 24 Grey SRS | Overall Survival (OS) | Strata C: Large tumor, resected | 5 Participants |
| Arm 1 - 24 Grey SRS | Overall Survival (OS) | Strata A: Small tumor, resected | 3 Participants |
| Arm 2 - 27 Grey SRS | Overall Survival (OS) | Strata C: Large tumor, resected | 2 Participants |
| Arm 2 - 27 Grey SRS | Overall Survival (OS) | Strata A: Small tumor, resected | 4 Participants |
| Arm 3 - 30 Grey SRS | Overall Survival (OS) | Strata C: Large tumor, resected | 4 Participants |
| Arm 3 - 30 Grey SRS | Overall Survival (OS) | Strata A: Small tumor, resected | 3 Participants |
| Arm 4 - 33 Grey SRS | Overall Survival (OS) | Strata C: Large tumor, resected | 2 Participants |
| Arm 4 - 33 Grey SRS | Overall Survival (OS) | Strata A: Small tumor, resected | 5 Participants |