Trial Outcomes & Findings for Optimal Planning Target Volume With Stereotactic Radiosurgery (NCT NCT01017497)

NCT ID: NCT01017497

Last Updated: 2015-02-13

Results Overview

The 12-month local control rate is the percentage of lesions without recurrence at the lesion site 12 months after SRS. Time to local recurrence was defined as the time between SRS and local recurrence. If local recurrence did not occur, the time to local recurrence was censored at last follow-up (including deaths without local recurrence). Kaplan-Meier methods were used to describe the time to local recurrence.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

49 participants

Primary outcome timeframe

12 months after SRS

Results posted on

2015-02-13

Participant Flow

Participant milestones

Participant milestones
Measure
Optimal PTV
Optimal Planning Target Volume with Stereotactic Radiosurgery
Overall Study
STARTED
49
Overall Study
COMPLETED
49
Overall Study
NOT COMPLETED
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Optimal Planning Target Volume With Stereotactic Radiosurgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Optimal PTV
n=49 Participants
Optimal Planning Target Volume with Stereotactic Radiosurgery
Age, Continuous
61 years
n=5 Participants
Sex: Female, Male
Female
33 Participants
n=5 Participants
Sex: Female, Male
Male
16 Participants
n=5 Participants

PRIMARY outcome

Timeframe: 12 months after SRS

Population: This is a lesion-specific outcome. A patient could have 1 lesion randomized to the 1mm arm and a different lesion randomized to the 3mm arm, the total participants analyzed will not equal 49. Of the 80 lesions, 4 of 40 lesions in the 1-mm arm and 7 of 40 in the 3-mm arm had insufficient post-SRS imaging data to be included in this analysis.

The 12-month local control rate is the percentage of lesions without recurrence at the lesion site 12 months after SRS. Time to local recurrence was defined as the time between SRS and local recurrence. If local recurrence did not occur, the time to local recurrence was censored at last follow-up (including deaths without local recurrence). Kaplan-Meier methods were used to describe the time to local recurrence.

Outcome measures

Outcome measures
Measure
1mm Margin
n=36 Lesion
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
n=33 Lesion
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
12-month Local Control Rate
91.4 percentage of lesions
Interval 67.7 to 98.0
95.2 percentage of lesions
Interval 70.7 to 99.3

SECONDARY outcome

Timeframe: 24 months after SRS

Population: This is a lesion-specific outcome. A patient could have 1 lesion randomized to the 1mm arm and a different lesion randomized to the 3mm arm, the total participants analyzed will not equal 49. Of the 80 lesions, 4 of 40 lesions in the 1-mm arm and 7 of 40 in the 3-mm arm had insufficient post-SRS imaging data to be included in this analysis.

The rate of radionecrosis is defined as the proportion of lesions with an indication of radiation-associated changes but no evidence of viable tumor on follow-up imaging (and confirmed by tissue biopsy whenever possible).

Outcome measures

Outcome measures
Measure
1mm Margin
n=36 Lesion
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
n=33 Lesion
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Rate of Radionecrosis at SRS Treatment Site
0.0278 proportion of lesions
Interval 0.0007 to 0.1453
0.1515 proportion of lesions
Interval 0.0511 to 0.319

SECONDARY outcome

Timeframe: 12 month after SRS

Population: The rate of distant brain metastases is a patient-specific outcome. Of the 49 patients enrolled, six had insufficient post-SRS imaging data to be included in this analysis.

The 12-month rate of distant brain metastases is defined as the percentage of participants with the appearance of new brain metastasis located away from the previously treated lesion (i.e. distant brain failure) 12 months after SRS. Time to the appearance of new brain metastasis was defined as the time between SRS and distant brain failure. Patients without new distant brain metastases as of the last follow-up were censored at the last follow-up date. Kaplan-Meier methods were used to describe the time to distant brain failure.

Outcome measures

Outcome measures
Measure
1mm Margin
n=43 Participants
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
12 Month Rate of Distant Brain Metastases
45.7 percentage of participants
Interval 28.9 to 61.1

SECONDARY outcome

Timeframe: 24 months after SRS

Overall survival was defined as the time in months from the start of SRS to the date of death or last contact if alive. Kaplan-Meier methods were used to estimate overall survival.

Outcome measures

Outcome measures
Measure
1mm Margin
n=49 Participants
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Median Overall Survival
10.6 months
Interval 6.1 to 14.4

SECONDARY outcome

Timeframe: Baseline to 3 months after SRS

Population: Only 24 patients of 49 enrolled completed both the baseline and month 3 questionnaire.

Quality of life as measured by the change in FACT-Br scores from baseline to 3 months after SRS. The FACT-Br (version 4) is comprised of the Functional Assessment of Cancer Therapy-General (FACT-G), a 27-item core questionnaire evaluating the domains of physical, family/social, emotional and functional well-being, with the addition of 23 brain cancer specific questions. The FACT-G total score is the sum of the four FACT-G domain scores. The Brain Cancer Subscale (BrCS) is the sum of 19 brain cancer specific questions. The FACT-Br Trial Outcome Index (TOI) is the sum of the BrCS score and the physical and family/social domain scores. The FACT-Br total score is the sum of the FACT-G total score and the BrCS score. Change score = score at 3 months after SRS - score at baseline. Positive change scores indicate improved quality of life.

Outcome measures

Outcome measures
Measure
1mm Margin
n=24 Participants
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-G: Physical Well-being (range: 0-28)
-3.2 Change in score from baseline to 3 month
Standard Error 1.2
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-G: Family/Social Well-being (range: 0-28)
-0.4 Change in score from baseline to 3 month
Standard Error 0.6
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-G: Emotional Well-being (range: 0-24)
0.6 Change in score from baseline to 3 month
Standard Error 0.9
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-G: Functional Well-being (range: 0-28)
-1.5 Change in score from baseline to 3 month
Standard Error 1.5
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-G: Total Score (range: 0-108)
-4.5 Change in score from baseline to 3 month
Standard Error 3.3
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-Br: BrCS (range: 0-76)
-1.3 Change in score from baseline to 3 month
Standard Error 3.2
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-Br: TOI (range: 0-132)
-6.0 Change in score from baseline to 3 month
Standard Error 5.3
Quality of Life at 3 Months After SRS as Measured by the Functional Assessment of Cancer Therapy-Brain (FACT-Br)
FACT-Br: Total Score (range: 0-184)
-5.8 Change in score from baseline to 3 month
Standard Error 6.1

SECONDARY outcome

Timeframe: Baseline to 3 months after SRS

Population: Only 24 patients of 49 enrolled completed both the baseline and month 3 questionnaire.

Cognition as measured by the change in MMSE scores from baseline to 3 months after SRS. The MMSE is an 11-item measure that tests five areas of cognitive function: orientation, registration, attention and calculation, recall and language. The minimum score is 0 and teh maximum score is 30 with higher MMSe scores indicating better cognition. Change score = score at 3 months after SRS - score at baseline. Positive change scores indicate improved cognition.

Outcome measures

Outcome measures
Measure
1mm Margin
n=24 Participants
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Cognition at 3 Months After SRS as Measured by the Mini-Mental State Exam (MMSE)
0.3 Change in score from baseline to 3 month
Standard Error 0.3

SECONDARY outcome

Timeframe: Baseline to 3 months after SRS

Population: Only 24 patients of 49 enrolled completed both the baseline and month 3 questionnaire.

Cognition as measured by the change in scores on the Trail Making Test (TMT) from baseline to 3 months after SRS. The TMT consists of two parts. Part A (TMT-A) requires an individual to draw lines sequentially connecting 25 encircled numbers distributed on a sheet of paper. Task requirements are similar for Part B (TMT-B) except the person must alternate between numbers and letters (e.g., 1, A, 2, B, 3, C, etc.). The score on each part represents the amount of time required to complete the task. Change score = score at 3 months after SRS - score at baseline. Negative change scores indicate improved cognition.

Outcome measures

Outcome measures
Measure
1mm Margin
n=24 Participants
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Cognition at 3 Months After SRS as Measured by the Trail Making Test (TMT)
TMT-A
-1.9 Change in seconds baseline to 3 months
Standard Error 3.1
Cognition at 3 Months After SRS as Measured by the Trail Making Test (TMT)
TMT-B
-19.9 Change in seconds baseline to 3 months
Standard Error 13.7

SECONDARY outcome

Timeframe: 24 months after SRS

The rate of death due to neurologic causes is defined as the percentage of participants whose death is attributable to the progression of neurological disease.

Outcome measures

Outcome measures
Measure
1mm Margin
n=49 Participants
GTV expanded by 1 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
3mm Margin
GTV expanded by 3 mm Stereotactic Radiosurgery: PTV Diameter \< 2.0 cm receives 24 Gy; PTV Diameter 2.0-3.0 cm receives 18 Gy; PTV Diameter 3.1-4.0 cm receives 15 Gy;
Rate of Death Due to Neurologic Causes
0.0 percentage of participants

Adverse Events

Optimal PTV

Serious events: 8 serious events
Other events: 29 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Optimal PTV
n=49 participants at risk
Optimal Planning Target Volume with Stereotactic Radiosurgery
Endocrine disorders
Adrenal insufficiency
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders
Abdominal pain
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Hepatobiliary disorders
Hepatic failure
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Central nervous system necrosis
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Intracranial hemorrhage
4.1%
2/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Peripheral motor neuropathy
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Syncope
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Tremor
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Other adverse events

Other adverse events
Measure
Optimal PTV
n=49 participants at risk
Optimal Planning Target Volume with Stereotactic Radiosurgery
Endocrine disorders
Cushingoid
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Eye disorders
Blurred vision
12.2%
6/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders
Diarrhea
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders
Fecal incontinence
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders
Nausea
8.2%
4/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Gastrointestinal disorders
Vomiting
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
General disorders
Edema limbs
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
General disorders
Fatigue
22.4%
11/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
General disorders
Gait disturbance
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
General disorders
Pain
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Infections and infestations
Vulval infection
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders
Anorexia
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Metabolism and nutrition disorders
Hyperglycemia
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Musculoskeletal and connective tissue disorders
Neck pain
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Ataxia
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Cognitive disturbance
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Dizziness
14.3%
7/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Dysphasia
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Headache
34.7%
17/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Memory impairment
6.1%
3/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Paresthesia
4.1%
2/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Peripheral sensory neuropathy
4.1%
2/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Nervous system disorders
Tremor
6.1%
3/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Psychiatric disorders
Confusion
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Psychiatric disorders
Insomnia
4.1%
2/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.
Respiratory, thoracic and mediastinal disorders
Dyspnea
2.0%
1/49 • 24 months
The adverse events for this study were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, and have been converted to CTCAE version 4.0 for entry into ClinicalTrials.gov.

Additional Information

John Kirkpatrick MD

Duke University Medical Center

Phone: 919 6687342

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place