Neoplasm Metastasis
Conditions
Keywords
Secondary brain malignancies, RapidArc, Volumetric modulated arc therapy
Brief summary
Brain metastases are the most common adult intracranial tumor, occurring in approximately 10% to 30% of adult cancer patients, and represent an important cause of morbidity and mortality. The most widely used treatment for patients with multiple brain metastases is whole brain radiation therapy (WBRT). The use of WBRT after resection or stereotactic radiosurgery (SRS) has been proven to be effective in terms of improving local control of brain metastases. RapidArc (RA) (Varian Medical Systems, Palo Alto, CA) is a new method of delivering radiation that uses arcs to deliver highly conformal intensity modulated three dimensional dose distributions. The purpose of this investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis. Given the limitations of the SRS boost technique, the purpose of our investigation is to evaluate an alternative strategy for giving WBRT with highly focal boost to gross visible lesions in patients with brain metastasis. In this study, we plan to assess the tolerability of using volumetric modulated arc therapy (RapidArc) on patients with brain metastasis to simultaneously treat the entire brain with a concomitant focal boost to grossly identified lesions on MRI scan to try to improve local control and reduce neurocognitive toxicities. This previous version of this study was a phase I dose escalation trial giving 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease. Prior to this, patients were enrolled onto one of two cohorts with whole brain dose of 30 Gy in 10 fractions with SIB to total of 45 Gy in 10 fractions to gross brain metastatic disease or whole brain dose of 37.5 Gy in 15 fractions with SIB to total of 52.5 Gy in 15 fractions to gross brain metastatic disease. A total of 12 patients have been previously enrolled on this trial. No patients have experienced a dose limiting toxicity (grade 3 or above) at least possibly due to study therapy. Also, no patients experienced local brain failure/progression at a site of treated metastatic brain disease. Based on this, we no longer feel that dose escalation to the gross brain disease is warranted and would proceed with a single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.
Interventions
RADIATIONVolumetric modulated arc therapy
Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy.
Sponsors
Emory University
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
* Pathologic proven diagnosis of solid tumor malignancy. * Age ≥ 18. * KPS ≥ 70. * Mini Mental Status Exam (MMSE) ≥ 18 prior to study entry. * RPA class I (KPS ≥ 70, primary cancer controlled, age \< 65, metastases in brain only) or class II (lack of one or more of class I criteria). * One to ten brain metastatic lesions.
Exclusion criteria
* Previous whole brain radiation therapy. * Previous radiosurgery to any currently progressive gross metastatic disease. * Previous radiosurgery to any intracranial site within the prior 6 weeks. * Recursive partitioning analysis (RPA) class III (KPS \< 70). * Radiosensitive (eg. small cell lung carcinomas, germ cell tumors, leukemias, or lymphomas) or unknown tumor histologies. * Concurrent chemotherapy (no chemotherapy starting 14 days before start of radiation). * Evidence of leptomeningeal disease by MRI and/or cerebrospinal fluid (CSF) cytology. * Current pregnancy. * No metastases to brain stem, midbrain, pons, or medulla or within 7 mm of the optic apparatus (optic nerves and chiasm).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients | Locoregional control at 1 year | The cumulative incidences of recurrence locally and in the whole brain were reported at the patient level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Brain Progression-free Survival | 11 months median follow up period. | Defined as period of time from study entry to to death from any cause or brain tumor recurrence or progression. |
| Overall Survival | 11 months median follow up period. | Defined time from study entry to death from any cause. |
| Neurocognitive Effects | 11 months median follow up period. | Neurological test score were assessed using the Hopkins Verbal Learning Test-Revised (HVLT). In the HVLT 12 words are read and the participant is asked to recall them, this is completed 3 times. Total words recalled are summed to give a score for Total Recall (0-36, higher scores demonstrated better recall). Delayed recall is conducted 20-25 minutes later on the same list of 12 words (scored 0-12 with higher scores demonstrating better recall). Retention is calculated as the percent of words recalled (scored 0-100, higher scores representing better recall). Recognition Discrimination is tested by a series of yes/no responses from the participant identifying 12 target words from a list of 24 and calculated by the number of true positives minus the number of true negatives with higher scores indicating a better outcome. |
| Quality of Life as Measured by the FACT-Br Subscales | 11 month median follow up | The Functional Assessment of Cancer Therapy-Brain (FACT-Br) were summed to create the FACT brain trial outcome index (FACT-BR TOI), FACT general (FACT-G), and FACT brain total (FACT-BR Total). Three FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient. FACT BR TOTAL (FACT-G + BrCS, possible range 0 - 200) FACT-BR TOI (Trial Outcome Index = Physical Well Being \_ Functional Well Being +BrCS, possible range 0 - 148) FACT-G (Fact General, possible range 0 - 108) |
Countries
United States
Participant flow
Recruitment details
Patients were recruited at Winship Cancer Institute of Emory University from September 2010 to September 2015.
Participants by arm
| Arm | Count |
|---|---|
| Volumetric Modulated Arc Therapy Single arm pilot study treating patients with 25 Gy in 10 fractions to the whole brain with simultaneous infield boost (SIB) to a total of 45 Gy in 10 fractions to gross brain metastatic disease.
Volumetric modulated arc therapy: Using volumetric modulated arc therapy to give simultaneous infield boost to gross metastatic brain lesions during whole brain radiation therapy. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Volumetric Modulated Arc Therapy |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 9 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 10 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 | 12 Participants |
| Region of Enrollment United States | 22 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 10 / 13 |
| other Total, other adverse events | 13 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients
The cumulative incidences of recurrence locally and in the whole brain were reported at the patient level.
Time frame: Locoregional control at 1 year
Population: Feasibility by our criteria was met for all participants.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Volumetric Modulated Arc Therapy | Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients | 1-year Local Control | 92 percentage of participants |
| Volumetric Modulated Arc Therapy | Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients | Lesion Level Control | 98.6 percentage of participants |
| Volumetric Modulated Arc Therapy | Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients | 1-year Regional Control | 46 percentage of participants |
| Volumetric Modulated Arc Therapy | Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients | Distant Intracranial Recurrence | 87.5 percentage of participants |
| Volumetric Modulated Arc Therapy | Percent of Participants With Locoregional Control of Treating Brain Metastasis Patients | Intracranial Control | 46 percentage of participants |
Secondary
Brain Progression-free Survival
Defined as period of time from study entry to to death from any cause or brain tumor recurrence or progression.
Time frame: 11 months median follow up period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volumetric Modulated Arc Therapy | Brain Progression-free Survival | 5.7 months |
Secondary
Neurocognitive Effects
Neurological test score were assessed using the Hopkins Verbal Learning Test-Revised (HVLT). In the HVLT 12 words are read and the participant is asked to recall them, this is completed 3 times. Total words recalled are summed to give a score for Total Recall (0-36, higher scores demonstrated better recall). Delayed recall is conducted 20-25 minutes later on the same list of 12 words (scored 0-12 with higher scores demonstrating better recall). Retention is calculated as the percent of words recalled (scored 0-100, higher scores representing better recall). Recognition Discrimination is tested by a series of yes/no responses from the participant identifying 12 target words from a list of 24 and calculated by the number of true positives minus the number of true negatives with higher scores indicating a better outcome.
Time frame: 11 months median follow up period.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Volumetric Modulated Arc Therapy | Neurocognitive Effects | Total Recall | 1.0 fraction of post-tx over pre-tx scores |
| Volumetric Modulated Arc Therapy | Neurocognitive Effects | Delayed Recall | 1.09 fraction of post-tx over pre-tx scores |
| Volumetric Modulated Arc Therapy | Neurocognitive Effects | Retention | 0.99 fraction of post-tx over pre-tx scores |
| Volumetric Modulated Arc Therapy | Neurocognitive Effects | Recognition Discrimination | 0.96 fraction of post-tx over pre-tx scores |
Secondary
Overall Survival
Defined time from study entry to death from any cause.
Time frame: 11 months median follow up period.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Volumetric Modulated Arc Therapy | Overall Survival | 8.6 months |
Secondary
Quality of Life as Measured by the FACT-Br Subscales
The Functional Assessment of Cancer Therapy-Brain (FACT-Br) were summed to create the FACT brain trial outcome index (FACT-BR TOI), FACT general (FACT-G), and FACT brain total (FACT-BR Total). Three FACT scales were calculated. The higher the value the better the score, i.e., the better the quality of life perceived by patient. FACT BR TOTAL (FACT-G + BrCS, possible range 0 - 200) FACT-BR TOI (Trial Outcome Index = Physical Well Being \_ Functional Well Being +BrCS, possible range 0 - 148) FACT-G (Fact General, possible range 0 - 108)
Time frame: 11 month median follow up
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Volumetric Modulated Arc Therapy | Quality of Life as Measured by the FACT-Br Subscales | FACT-BR Total | 1.0 fraction of post-tx over pre-tx scores |
| Volumetric Modulated Arc Therapy | Quality of Life as Measured by the FACT-Br Subscales | FACT-BR TOI | 0.98 fraction of post-tx over pre-tx scores |
| Volumetric Modulated Arc Therapy | Quality of Life as Measured by the FACT-Br Subscales | FACT-G | 0.98 fraction of post-tx over pre-tx scores |