Brain Metastases
Conditions
Keywords
Demonstrate coordination of HBO with SRS treatments is feasible., Demonstrate outcomes for patients treated with combination of HBO and SRS are non-inferior .
Brief summary
Patients with brain metastases who are candidates for treatment with stereotactic radiosurgery (SRS) are potential study participants. SRS delivers high-energy, precisely-focused radiation to each brain metastasis to shrink the tumor, and is the standard-of-care for patients with these tumors. Oxygen enhances the damaging effects of radiation on tumor cells. Hyperbaric oxygen (HBO) therapy increases oxygen levels in all kinds of tissues, including tumors. The purpose of this trial is to study whether it is feasible to treat patients with HBO just prior to receiving SRS, given the timing constraints of treating sequentially with HBO and then SRS. Patients will undergo HBO treatment followed by the placement of a Gill-Thomas-Cosman head frame then transported ,via stretcher, to receive SRS. The transfer and placement of the head frame needs to be completed within the 15minute time frame. The trial's secondary objectives are to determine whether it has any effects on outcomes and quality of life. As part of study participation patients will be asked to complete quality of life questionnaires as well as mini mental status questionnaires. These will be done prior to treatment and at follow up appointments throughout the next 3 years while participating in the study. Patients will be given the option to participate in the optional bio marker blood draw study which would require patients to have blood drawn at three time points, pre-treatment, the day after treatment and at their first follow up visit.
Interventions
DEVICEHyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO
Sponsors
Dartmouth-Hitchcock Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Metastatic brain tumor referred to radiation oncology for treatment * Size of the presenting metastatic lesion up to 5.0 cm diameter * Age \> 18 years * Patients must give informed consent indicating they are aware of the investigational nature of this treatment * Karnofsky Performance Status \> 70% (Zubrod score 0 to 1) * Women of childbearing potential must have a negative serum or urine pregnancy test within 14 days to start of study therapy * CBC and CMP within 30 days to start of study therapy * Chest imaging (Chest Xray or Chest CT) within past 12 months, that does not show any contraindication to hyperbaric therapy (if patient has had any thoracic surgery or other significant event that might have affected the thorax such as trauma, pneumothorax, chest tube insertion, pleurodesis, or thoracentesis and has not had imaging since that event, then the imaging should be repeated). * Neurosurgery Consult
Exclusion criteria
* Pregnant women or women of childbearing potential without adequate contraception. Contraception, which can include abstinence, is required since the last menstrual period until completion of SRS. * Evidence of pneumothorax (Untreated pneumothorax risks tension pneumothorax during ascent in HBO chamber) * COPD with C02 retention (Such patients can develop respiratory depression as HBO reduces their hypoxemic drive) * Uncontrolled seizure disorder (Note that patients on adequate antiepileptic medications may receive HBO) * Claustrophobia resistant to medication (Pre-medication with anxiolytics is generally sufficient for almost all anxious patients undergoing HBO treatment) * History of middle ear surgery * Failure to equalize pressure in the middle ear can cause displacement of middle ear structures with consequent hearing loss * To clarify: placement of a tympanostomy tube is not a contraindication to HBO, and in fact may improve tolerability of the procedure * History of bleomycin administration (HBO can exacerbate interstitial pneumonitis in such patients) * Current cis-platinum chemotherapy, i.e. therapeutic levels in the bloodstream at the time of HBO therapy. (HBO can increase cytotoxicity of cis-platinum) * Uncontrolled high blood pressure (HBO can increase systemic vascular resistance) * Unstable angina or myocardial infarction within the previous 3 months (Increased afterload due to HBO can increase myocardial workload) * Cardiac EF ≤ 35% * Pulmonary edema can arise with HBO in certain patients with severe heart failure * In patients with prior history of CHF, subsequent echocardiogram and ECG are required to establish EF\>35% * Treatment with disulfiram (Disulfiram inhibits superoxide dismutase and is not approved for use concomitantly with hyperbaric oxygen therapy) * Active drug/alcohol dependence or abuse * Lack of adequate social support structures, e.g. homelessness * Tumors with potential confounding results on serum marker studies * Small cell (neuroendocrine) carcinomas * Carcinoid tumors
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Average Time From HBO Chamber Exit to SRS beam-on | Approximately 30 minutes during SRS Treatment Visit | Time from end of HBO decompression to start of SRS treatment will be measured to determine feasibility. Feasibility is defined as having been achieved if more than 50% of the 20 evaluable patients start SRS treatment within 30 minutes of leaving the HBO tank |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Years Until Local Recurrence Prior to WBRT | 5 year from treatment | Number of years until local recurrence of lesion prior to whole brain radiation therapy |
| Number of Participants Developing Intercranial Distant Recurrence | 5 year from treatment | Number of participants who developed intercranial distant recurrence |
| Number of Months Between SRS Treatment and Whole Brain Radiation Therapy | 5 year from treatment | — |
| Number of Lesions Exhibiting Radionecrosis | 5 year from treatment | — |
| Overall Survival in Years | 5 year from treatment | Median time to death |
| Number of Years Until Local Recurrence | 5 year from treatment | Number of years until recurrence of lesion |
Other
| Measure | Time frame | Description |
|---|---|---|
| Presence of S100 and NSE (Serum Markers for Tissue Apoptosis and for Neuronal Damage) | 24-48 hours after the SRS treatment | Serum markers for tissue apoptosis and for neuronal damage |
| Average Score of Quality of Life as Measured by St. Louis University Mental Status Exam (SLUMS) Mental Status Exam (SLUMS) | Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years | SLUMS is an 11-item screening tool to evaluate cognitive ability in adults. The SLUMS score ranges from 1-30. For patients with a high school education, the normal range score is 27-30. For mild neurocognitive disorder, the score range is 21-26. Dementia range is 1-20. For patients with less than a high school education the normal range score is 25-30. For mild neurocognitive disorder, the score range is 20-24. Dementia range is 1-19. The scores across all time points were averaged to obtain the mean. |
| Average Score of EORTC Global Health Status (QL2) | Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years | Averages score QL2 determined by responses to aggregate combined results of questionnaires (QLQ C-30 and BN-20). EORTC Quality of Life Questionnaire C-30 (QLQ C-30): 30-item self-report questionnaire rating items on a 4-point scale (1 not at all to 4 very much) It measures several domains (physical, role, emotional, cognitive, and social functioning, fatigue, pain, nausea and vomiting) and several single items. Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better QoL on global health status and functional scales and worse QoL on symptom scales and financial difficulty scale. EORTC QLQ BN-20 (BN-20): 4 scales comprised of multiple items and 7 single items. All items are rated on a 4-point Likert-type scale, 1=not at all' to 4=very much, and linearly transformed to a 0-100 scale, higher scores indicating more severe symptoms. The scores across all time points were averaged to obtain the mean. |
Countries
United States
Participant flow
Recruitment details
HBO feasibility subjects were recruited from potential candidates for stereotactic radiosurgery (SRS) treatment at DHMC for brain metastases. Such patients are referred to radiation oncology by practitioners at DHMC and by physicians at outlying hospitals. Historic Controls: Retrospective review of previous patients utilizing SRS in the treatment of brain metastases. The control population was selected based on matching variables.
Pre-assignment details
Adverse events were not collected for historic controls.
Participants by arm
| Arm | Count |
|---|---|
| HBO Feasibility Hyperbaric oxygen given at 2.4 ATA for 30 minutes immediately prior to SRS - HBOT for 30 minutes - SRS without prior HBO. Demographic information (Race, gender, ethnicity, and age) were collected for only the participants who were prospectively enrolled and provided informed consent. | 22 |
| Historic Controls Retrospective review of previous patients utilizing SRS in the treatment of brain metastases. The matching variables (histology, lesion size, resection status, and calculated GPA) will be used to identify this control population. | 19 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Not eligible | 3 | 0 |
Baseline characteristics
| Characteristic | HBO Feasibility | Historic Controls | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 9 Participants | 15 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants | 10 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 0 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 19 Participants | 19 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 19 Participants | 19 Participants |
| Race (NIH/OMB) White | 22 Participants | 0 Participants | 22 Participants |
| Region of Enrollment United States | 22 participants | 19 participants | 41 participants |
| Sex: Female, Male Female | 15 Participants | 10 Participants | 25 Participants |
| Sex: Female, Male Male | 7 Participants | 9 Participants | 16 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 19 | 0 / 19 |
| other Total, other adverse events | 5 / 19 | 6 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
The Average Time From HBO Chamber Exit to SRS beam-on
Time from end of HBO decompression to start of SRS treatment will be measured to determine feasibility. Feasibility is defined as having been achieved if more than 50% of the 20 evaluable patients start SRS treatment within 30 minutes of leaving the HBO tank
Time frame: Approximately 30 minutes during SRS Treatment Visit
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| HBO Feasibility | The Average Time From HBO Chamber Exit to SRS beam-on | 8.3 minutes |
Secondary
Number of Lesions Exhibiting Radionecrosis
Time frame: 5 year from treatment
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| HBO Feasibility | Number of Lesions Exhibiting Radionecrosis | 5 Lesions exhibiting radionecrosis |
| Historic Controls | Number of Lesions Exhibiting Radionecrosis | 6 Lesions exhibiting radionecrosis |
p-value: 0.76Kaplan-Meier
Secondary
Number of Months Between SRS Treatment and Whole Brain Radiation Therapy
Time frame: 5 year from treatment
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. 17 participants in the HBO group, and 14 historical controls did not receive whole brain radiation therapy
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBO Feasibility | Number of Months Between SRS Treatment and Whole Brain Radiation Therapy | 8.5 Months |
| Historic Controls | Number of Months Between SRS Treatment and Whole Brain Radiation Therapy | 5.6 Months |
Secondary
Number of Participants Developing Intercranial Distant Recurrence
Number of participants who developed intercranial distant recurrence
Time frame: 5 year from treatment
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| HBO Feasibility | Number of Participants Developing Intercranial Distant Recurrence | 9 Participants |
| Historic Controls | Number of Participants Developing Intercranial Distant Recurrence | 11 Participants |
p-value: 0.76Kaplan-Meier
Secondary
Number of Years Until Local Recurrence
Number of years until recurrence of lesion
Time frame: 5 year from treatment
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBO Feasibility | Number of Years Until Local Recurrence | NA Years |
| Historic Controls | Number of Years Until Local Recurrence | NA Years |
Secondary
Number of Years Until Local Recurrence Prior to WBRT
Number of years until local recurrence of lesion prior to whole brain radiation therapy
Time frame: 5 year from treatment
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBO Feasibility | Number of Years Until Local Recurrence Prior to WBRT | NA Years |
| Historic Controls | Number of Years Until Local Recurrence Prior to WBRT | NA Years |
Secondary
Overall Survival in Years
Median time to death
Time frame: 5 year from treatment
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| HBO Feasibility | Overall Survival in Years | 1.42 Years |
| Historic Controls | Overall Survival in Years | 1.03 Years |
Other Pre-specified
Average Score of EORTC Global Health Status (QL2)
Averages score QL2 determined by responses to aggregate combined results of questionnaires (QLQ C-30 and BN-20). EORTC Quality of Life Questionnaire C-30 (QLQ C-30): 30-item self-report questionnaire rating items on a 4-point scale (1 not at all to 4 very much) It measures several domains (physical, role, emotional, cognitive, and social functioning, fatigue, pain, nausea and vomiting) and several single items. Scores are averaged for each scale and transformed to 0-100 scale; higher score indicates better QoL on global health status and functional scales and worse QoL on symptom scales and financial difficulty scale. EORTC QLQ BN-20 (BN-20): 4 scales comprised of multiple items and 7 single items. All items are rated on a 4-point Likert-type scale, 1=not at all' to 4=very much, and linearly transformed to a 0-100 scale, higher scores indicating more severe symptoms. The scores across all time points were averaged to obtain the mean.
Time frame: Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. This information was not available for historical controls.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HBO Feasibility | Average Score of EORTC Global Health Status (QL2) | 66.8 score on a scale | Standard Deviation 24.6 |
Other Pre-specified
Average Score of Quality of Life as Measured by St. Louis University Mental Status Exam (SLUMS) Mental Status Exam (SLUMS)
SLUMS is an 11-item screening tool to evaluate cognitive ability in adults. The SLUMS score ranges from 1-30. For patients with a high school education, the normal range score is 27-30. For mild neurocognitive disorder, the score range is 21-26. Dementia range is 1-20. For patients with less than a high school education the normal range score is 25-30. For mild neurocognitive disorder, the score range is 20-24. Dementia range is 1-19. The scores across all time points were averaged to obtain the mean.
Time frame: Baseline, 4 to 6 weeks after treatment and then every 3 months for a minimum of 1 year, up to 5 years
Population: Three (3) participants were screen failures, and did not receive study treatment, and not included in the analysis. This information was not available for historical controls.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HBO Feasibility | Average Score of Quality of Life as Measured by St. Louis University Mental Status Exam (SLUMS) Mental Status Exam (SLUMS) | 26.5 units on a scale | Standard Deviation 3.4 |
Other Pre-specified
Presence of S100 and NSE (Serum Markers for Tissue Apoptosis and for Neuronal Damage)
Serum markers for tissue apoptosis and for neuronal damage
Time frame: 24-48 hours after the SRS treatment
Population: Sample donations where optional for the study participants. Insufficient samples were obtained and therefore, samples were not analyzed.