Anaplastic Astrocytoma, Astrocytoma, Glioblastoma, Glioma, Mixed Glioma, Mixed Oligoastrocytoma, Oligodendroglioma, Optic Glioma, Pilocytic Astrocytoma
Conditions
Brief summary
By employing a combination of advanced MRI techniques and correlative serum biomarkers of blood brain barrier (BBB) disruption, the investigators plan to develop a powerful, first of its kind clinical algorithm in pediatrics whereby the investigators can measure and identify the window of maximal BBB disruption post MLA to 1) allow for an alternative to surgery in incompletely resected tumors, 2) allow for optimal chemotherapeutic dosing to achieve the greatest benefits and the least systemic side effects and 3) distinguish subsequent tumor progression from long-term MLA treatment effects. Preliminary data in adult imaging studies have shown that the BBB disruption lasts for several weeks following treatment before returning to a low baseline. This pilot therapeutic study will provide preliminary validation in pediatric patients.
Interventions
DRUGDoxorubicin
DRUGEtoposide
DEVICEDynamic contrast-enhanced (DCE) MRI
DEVICEDynamic susceptibility contrast (DSC) MRI
Sponsors
Washington University School of Medicine
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
ARM A * Presumed pediatric gliomas (grades I-IV) on MRI that are determined to be candidates for MLA by the treating neurosurgeon * Age 3 to ≤ 21 * Karnofsky/Lansky performance status ≥ 60% ARM B * Recurrent pediatric brain tumors determined candidates for MLA as determined by the treating neurosurgeon. * Unequivocal evidence of tumor progression by MRI * There must be an interval of at least 12 weeks from the completion of radiotherapy to study registration except if there is unequivocal evidence for tumor recurrence per RANO criteria. When the interval is less than 12 weeks from the completion of radiotherapy, the use of PET scan is allowed to differentiate between evidence of tumor recurrence and pseudoprogression. * Recurrent lesions with dimension and contour that are determined by the treating neurosurgeon to be appropriate for MLA. * Age 3 to ≤ 21 * Karnofsky/Lansky performance status ≥ 60% * Adequate cardiac function as determined by a shortening fraction ≥ 27% or left ventricular ejection fraction ≥ 50% by echocardiogram within the past 1 year prior to registration. * Prior anthracycline therapy does not exceed 200 mg/m\^2 total cumulative dose. * Adequate bone marrow and hepatic function as defined below (must be within 7 days of MLA): * Absolute neutrophil count (ANC) ≥ 1000/mcl (G-CSF is allowed) * Platelets ≥ 100 K/cumm * Hemoglobin ≥ 9 g/dL (pRBC transfusion +/- ESA are allowed) * ALT ≤ 3 x ULN * AST ≤ 3 x ULN * ALP ≤ 3 x ULN. If ALP is \> 3 x ULN, GGT must be checked and be ≤ 3 x ULN. * Bilirubin ≤ 2 x ULN * At the time of registration, patient must have recovered from the toxic effects of prior therapy to no more than grade 1 toxicity. * At the time of registration, patient must be at least 4 weeks from other prior cytotoxic chemotherapy. * Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately. * Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).
Exclusion criteria
ARM A * Currently receiving or scheduled to receive any other therapies intended to treat the newly diagnosed glioma prior to MLA and the first post-MLA blood collection for correlative studies. * Multi-focal or metastatic disease. * Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine pregnancy test within 14 days of study entry. * Inability to undergo MRI due to personal or medical reasons. * Known history of HIV or autoimmune diseases requiring immunosuppressant drugs. ARM B * Prior treatment with bevacizumab within 12 weeks of study entry. * Previous treatment with complete cumulative doses of daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones that is equivalent to a total dose of \> 200 mg/m2 doxorubicin. * More than 2 prior relapses (not counting the current relapse being treated on this study). * Currently receiving any other investigational agents that are intended as treatments of the relapsed tumor. * Multi-focal or metastatic disease. * A history of allergic reactions attributed to compounds of similar chemical or biologic composition to doxorubicin or other agents used in the study. * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, recent heart attack within the previous 12 months or severe heart problems, or psychiatric illness/social situations that would limit compliance with study requirements. * Pregnant and/or breastfeeding. Premenopausal women must have a negative serum or urine pregnancy test within 14 days of study entry. * Inability to undergo MRI due to personal or medical reasons. * Known history of HIV or autoimmune diseases requiring immunosuppressant drugs.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Arm A Only: Number of Participants With Progression-free Survival (PFS) | Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days) | PFS is followed from start of treatment to time of progression or death, whichever occurs first. |
| Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years | Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days) | — |
| Arm B Only: Number of Participants With Progression-free Survival (PFS) | At 6 months | PFS is followed from start of treatment to time of progression or death, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B) | * Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * The glial fibrillary acidic protein (GFAP) is a classic intermediate filament protein specific to astrocytes in the CNS. GFAP is characteristic of astrocyte- and neural stem cell-derived gliomas in CNS tumors and is used to identify malignancies of glial origin, such as astrocytomas and GBM. Serum GFAP values can be increased with temporal disruption of BBB post-MLA. |
| Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | At 1 year post-MLA | Score ranges from 100% to 10%. A higher score indicates that the patient has a more normal quality of life. |
| Predictive Value of the Peritumoral Permeability Score for Patient Outcome as Measured by PFS | 6 months | Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data (as measured by 6 month PFS rate) to determine whether it has a predictive value. |
| Correlation of MR Imaging With Peritumoral BBB Disruption | 1 year from MLA | The linear regression model will used to investigate the correlation between MR imaging and peritumoral BBB disruption. To account for correlation among the repeated measures from the same patient, the longitudinal data will be analyzed with the use of linear generalized estimating equation (GEE). Whether the average measurements differ at the multiple time points will be evaluated through GEE model. Least-square means at each time points will be presented and standard errors will be calculated within the use of the GEE sandwich method when accounting for within-patient correlation. |
| Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B) | * Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * Neuron specific enolase is an enzyme involved in glycolysis, which is localized in neurons and axonal processes. Potentially, it escapes into the blood and CSF at the time of neural injury. Elevated serum NSE seemed to correlates with disruption in BBB following MLA and transient increase in BBB permeability. |
| Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B) | * Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * S100b is a low-molecular-weight Calcium-binding protein primarily found in astrocytic glial cells of the CNS. It is secreted by astrocytes for neuroprotective and -trophic cellular functions in the CNS. Elevated serum values can be associated with temporal changes in BBB integrity following MLA. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Arm A (MRI-guided Laser Ablation) * MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim.
* Participants will undergo DCE and DSC-MRI imaging at the following time points:
* no more than 3 weeks prior to MLA (OPTIONAL)
* within approximately 4 days after MLA
* 2-4 weeks after MLA
* Every 12 weeks (+/- 7 days) for the first year or until disease progression | 5 |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) * MLA is a minimally invasive laser surgery currently FDA approved for cytoreductive treatment of brain tumors, both primary and metastatic. MLA employs a small incision in the scalp and skull, through which a thin laser probe is inserted and guided by MR imaging to the core of a tumor mass where it delivers hyperthermic ablation from the core to the rim.
* Within 7 days of MLA (range 2-14 days) doxorubicin will be given intravenously on an outpatient basis weekly for 6 weeks at a dose of 25 mg/m\^2 over 5-30 minutes
* Following the completion of doxorubin, etoposide 50 mg/m\^2/day will be given orally for 21 days of each 28-day cycle (treatment can continue up to 24 cycles)
* Participants will undergo DCE and DSC-MRI imaging at the following time points:
* no more than 3 weeks prior to MLA (OPTIONAL)
* within approximately 4 days after MLA
* 2-4 weeks after MLA
* every 8 weeks (+/- 7 days) until 2 years have elapsed or disease progression, whichever comes first | 1 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Disease progression | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 0 |
Baseline characteristics
| Characteristic | Arm A (MRI-guided Laser Ablation) | Total | Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) |
|---|---|---|---|
| Age, Continuous | 11 years | 11.5 years | 12 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 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 | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 4 Participants | 5 Participants | 1 Participants |
| Region of Enrollment United States | 5 participants | 6 participants | 1 participants |
| Sex: Female, Male Female | 2 Participants | 2 Participants | 0 Participants |
| Sex: Female, Male Male | 3 Participants | 4 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 1 |
| other Total, other adverse events | 5 / 5 | 0 / 1 |
| serious Total, serious adverse events | 0 / 5 | 0 / 1 |
Outcome results
Primary
Arm A Only: Number of Participants With Progression-free Survival (PFS)
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Time frame: Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
Population: This outcome measure is for Arm A participants only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (MRI-guided Laser Ablation) | Arm A Only: Number of Participants With Progression-free Survival (PFS) | 4 Participants |
Primary
Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years
Time frame: Up to 5 years from date of registration (median length of follow-up, full range 196 days-1801 days)
Population: This outcome measure is for Arm A participants only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A (MRI-guided Laser Ablation) | Arm A Only: Overall Survival (OS) as Measured by Number of Participants Alive at 5 Years | 5 Participants |
Primary
Arm B Only: Number of Participants With Progression-free Survival (PFS)
PFS is followed from start of treatment to time of progression or death, whichever occurs first.
Time frame: At 6 months
Population: This outcome measure is for Arm B participants only.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Arm B Only: Number of Participants With Progression-free Survival (PFS) | 0 Participants |
Secondary
Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status
Score ranges from 100% to 10%. A higher score indicates that the patient has a more normal quality of life.
Time frame: At 1 year post-MLA
Population: This data was not collected on the patient from Arm B.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | Baseline | 90 score on a scale |
| Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | 1 year post-MLA | 90 score on a scale |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | Baseline | 100 score on a scale |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | 1 year post-MLA | 100 score on a scale |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | Baseline | 80 score on a scale |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | 1 year post-MLA | 80 score on a scale |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | 1 year post-MLA | 100 score on a scale |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | Baseline | 100 score on a scale |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | Baseline | 100 score on a scale |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Change in Quality of Life as Measured by Karnofsky or Lansky Performance Status | 1 year post-MLA | 100 score on a scale |
Secondary
Correlation of MR Imaging With Peritumoral BBB Disruption
The linear regression model will used to investigate the correlation between MR imaging and peritumoral BBB disruption. To account for correlation among the repeated measures from the same patient, the longitudinal data will be analyzed with the use of linear generalized estimating equation (GEE). Whether the average measurements differ at the multiple time points will be evaluated through GEE model. Least-square means at each time points will be presented and standard errors will be calculated within the use of the GEE sandwich method when accounting for within-patient correlation.
Time frame: 1 year from MLA
Population: Data was not collected for this outcome measure.
Secondary
Predictive Value of the Peritumoral Permeability Score for Patient Outcome as Measured by PFS
Biomarkers with higher correlation coefficient (r approaching 1) will be given higher priority. A minimum r=0.5 is required for inclusion for further analysis and will be used as a peritumoral permeability score. This score will then be correlated with the patient outcome data (as measured by 6 month PFS rate) to determine whether it has a predictive value.
Time frame: 6 months
Population: Data was not collected for this outcome measure.
Secondary
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP
* Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * The glial fibrillary acidic protein (GFAP) is a classic intermediate filament protein specific to astrocytes in the CNS. GFAP is characteristic of astrocyte- and neural stem cell-derived gliomas in CNS tumors and is used to identify malignancies of glial origin, such as astrocytomas and GBM. Serum GFAP values can be increased with temporal disruption of BBB post-MLA.
Time frame: Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)
Population: The one participant in Arm B did not consent to any procedures past 12 months post-MLA. There are time points not included because either the GFAP was not detected in the samples or the samples were not collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | 2-4 weeks | 0.0652591 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | Day 3 | 4.7370968 ng/ml |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | Day 3 | 1.6146649 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | Day 3 | 0.2225989 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | Day 3 | 5.6051762 ng/ml |
| Unknown | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | Baseline | — ng/ml |
| Unknown | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | 24 weeks | — ng/ml |
| Unknown | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | 12 weeks | — ng/ml |
| Unknown | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | 36 weeks | — ng/ml |
| Unknown | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in GFAP | 48 weeks | — ng/ml |
Secondary
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE)
* Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * Neuron specific enolase is an enzyme involved in glycolysis, which is localized in neurons and axonal processes. Potentially, it escapes into the blood and CSF at the time of neural injury. Elevated serum NSE seemed to correlates with disruption in BBB following MLA and transient increase in BBB permeability.
Time frame: Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)
Population: The one participant in Arm B did not consent to any procedures past 12 months post-MLA. There are time points not included because either the NSE was not detected in the samples or the samples were not collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 24 weeks | 19.1706 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Day 3 | 47.2666 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 36 weeks | 22.8186 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Baseline | 29.0219 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 48 weeks | 15.4708 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 2-4 weeks | 12.0186 ng/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 12 weeks | 105.7828 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 24 weeks | 7.8464 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 2-4 weeks | 53.2519 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Day 3 | 26.7537 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Baseline | 58.3406 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 12 weeks | 15.1011 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 48 weeks | 35.6507 ng/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 36 weeks | 7.9655 ng/ml |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 12 weeks | 7.5436 ng/ml |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Day 3 | 6.0443 ng/ml |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 2-4 weeks | 5.4452 ng/ml |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Baseline | 3.1823 ng/ml |
| Patient 3: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 24 weeks | 3.8632 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 36 weeks | 10.0722 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Baseline | 13.1819 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Day 3 | 33.8034 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 24 weeks | 5.5086 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 12 weeks | 206.8570 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 2-4 weeks | 11.4998 ng/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 48 weeks | 25.8530 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 48 weeks | 5.9343 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Baseline | 7.5534 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Day 3 | 17.4680 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 2-4 weeks | 9.3916 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 12 weeks | 13.5989 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 24 weeks | 13.8210 ng/ml |
| Patient 5: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 36 weeks | 5.9368 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 4 week | 5.7440 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Baseline | 11.5114 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 2 week | 8.6069 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 1 week | 11.5909 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | Day 3 | 18.5711 ng/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in Neuron-specific Enolase (NSE) | 14 weeks | 6.1692 ng/ml |
Secondary
Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B
* Arm A patients had blood drawn at the following time points: baseline, 3 days post-MLA, 2-4 weeks post-MLA, and every 12 weeks thereafter for 12 months post-MLA * Arm B patients had blood drawn at the following time points: baseline, 3 days post-MLA, week 1, week 2, week 3, week 4, week 5, week 6, and every 8 weeks for the first 2 years or until disease progression, whichever occurs first. * S100b is a low-molecular-weight Calcium-binding protein primarily found in astrocytic glial cells of the CNS. It is secreted by astrocytes for neuroprotective and -trophic cellular functions in the CNS. Elevated serum values can be associated with temporal changes in BBB integrity following MLA.
Time frame: Up to 48 weeks post MRI-guided laser heat ablation (Arm A) or up to 2 years post MRI-guided laser heat ablation (Arm B)
Population: The one participant in Arm B did not consent to any procedures past 12 months post-MLA. There are time points not included because either the S100B was not detected in the samples or the samples were not collected.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 12 weeks | 156.00 pg/ml |
| Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | Day 3 | 39.90 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 2-4 weeks | 55.74 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 48 weeks | 79.11 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | Day 3 | 58.86 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 36 weeks | 55.66 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | Baseline | 79.74 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 12 weeks | 59.78 pg/ml |
| Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 24 weeks | 65.91 pg/ml |
| Patient 4: Arm A (MRI-guided Laser Ablation) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | 12 weeks | 239.13 pg/ml |
| Patient 1: Arm B (MRI-guided Laser Ablation, Doxorubicin, Etoposide) | Serum Biomarkers of Peritumoral Blood Brain Barrier (BBB) Disruption as Measured by Change in S100B | Day 3 | 35.90 pg/ml |