Ignite Creation Date:
2024-05-05 @ 11:46 AM
Last Modification Date:
2024-10-26 @ 9:13 AM
Study NCT ID:
NCT00125697
Status:
COMPLETED
Last Update Posted:
2016-07-18
First Post:
2005-07-29
Brief Title:
Characterization of Serial Magnetic Resonance Spectroscopy Imaging in Patients With Malignant Glioma Undergoing Radiotherapy
Sponsor:
AHS Cancer Control Alberta
Organization:
AHS Cancer Control Alberta
Study Overview
Official Title:
Characterization of Serial Magnetic Resonance Spectroscopy Imaging in Patients With Malignant Glioma Undergoing Radiotherapy
Status:
COMPLETED
Status Verified Date:
2016-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Malignant glioma is the most common primary brain tumor in adults Despite aggressive therapy less than 40 of these patients are expected to live beyond 5 years The radiologic imaging of these tumors relies on computed tomography CT and magnetic resonance imaging MRI - these studies provide good anatomical information about the size and location of the tumor but are unable to evaluate whether the tumor is still viable or contains metabolic activity after surgery and in particular radiotherapy RT This complicates accurate understanding of the status of the tumor during a patients follow-up This study proposes to add magnetic resonance spectroscopy a non-invasive imaging method which can monitor metabolic changes in the tumor to regular imaging Understanding the changes that occur in a tumor over the course of radiotherapy could help predict how well a treatment might work and could also be useful in distinguishing a return of the tumor in an area of radiation damage before it would be obvious on regular imaging
Detailed Description:
Background
Malignant glioma is the most common primary brain tumor in adults Despite aggressive therapy less than 40 of these patients are expected to live beyond 5 years External beam radiotherapy following maximal surgical resection is the mainstay of treatment for this group of patients Recent intensification of local therapy with focused radiotherapy planning has resulted in successful escalation of dose Further improvement in the therapeutic index of therapy is desirable
Radiologic characterization of glial tumors relies predominantly on CT and MRI images these studies provide good anatomic information regarding the size and location of the tumor as well as surrounding structures but are unable to evaluate viability or proliferative activity of tumors Thus the enhancing lesion on CT or MRI may not correspond precisely to areas of viable tumor especially after surgery and radiotherapy Also because contrast enhanced MRI relies on regions of blood brain barrier BBB breakdown it is not tumor specific thus non-neoplastic processes may lead to findings similar to disease progression This phenomenon can make conventional radiologic follow-up difficult in patients who have received radiotherapy as such imaging techniques are limited in their ability to discern radiotherapy effect and necrosis from recurrence and progression Finally because they do not discriminate viable tumor CT and MRI are of limited usefulness in assessing response to therapy and are unable to effectively predict outcome Magnetic Resonance Spectroscopy MRS is a relatively new technology which may be able to address these issues
The objective of the current study is to investigate the changes that occur in tumor related magnetic resonance MR spectra over the course of radical radiotherapy for malignant glioma The primary endpoint for the study will be to identify characteristic evolving metabolite patterns on MRSI before during and after radiotherapy that correlate with overall survival and progression-free survival in high grade gliomas Secondary endpoints will involve correlation of MRSI metabolite patterns with time to progression and Karnofsky performance status
Eligibility Criteria
Patients must be older than 18 years of age
Patients must have histologically proven malignant glioma of the brain
Patients must have bi-directionally measurable enhancing residual disease by T1 weighted image
Patients must be willing to undergo high dose radiotherapy to the brain for the treatment of their glial tumor
Patients must be willing and able to comply with all study requirements
The patient or legally authorized representative must fully understand all elements of informed consent and sign the consent document
Ineligibility Criteria
Ineligibility criteria include
History of previous RT to the head and neck region
History of lupus scleroderma or RT hypersensitivity
Co-existing medical condition precluding radiotherapy
Psychiatric conditions precluding informed consent
Medical or psychiatric conditions precluding MR studies eg pacemaker aneurysm clips neuro stimulator cochlear implant severe claustrophobiaanxiety
Patients will be approached for study participation at the time of their initial radiation oncology consultation in the outpatient department of the Cross Cancer Institute CCI Patients who wish to participate and satisfy the eligibility and exclusion criteria will be required to review and sign the consent form at that time Patients will then undergo regular staging investigations construction of an immobilizing shell treatment planning MRI and CT simulation These studies are typically completed 2 weeks after the initial consult Radiotherapy will commence approximately 3-4 weeks after the initial consult At week 0 of RT prior to beginning therapy the patient will undergo the baseline MRS The mid-RT MRS study will be performed during week 4 of RT The post therapy scan will take place 2 months post-therapy From then on patients will be seen in clinic every 2-4 months for follow-up and will undergo MRI and MRS scans with each visit for 1 year
Data Collection and Statistical Analysis
The height of each MRS metabolite peak will be measured from voxels within the enhancing MRI lesion and from voxels in normal brain for each patient Relative metabolite values normalized to the value in normal brain will then be generated as well as relative metabolite ratios eg relative cholinerelative NAA for each time point week 0 week 4 and post-RT at follow-up For each patient the relative metabolite levels and ratios will be plotted over time Patients will then be partitioned into groups based on similar evolving MRS pattern For each of the groups curves of survival and disease free progression will be generated by the Kaplan-Meier method The curves will be analyzed for statistical significance by the log-rank method
The investigators plan to accrue 30 patients for the present study They are confident 30 patients will be sufficient to generate statistically significant results In a study of the effects of brain tumor radiotherapy on normal brain as imaged by NMR spectroscopy Urtasun et al were able to find statistically significant metabolite changes on proton MRS images with only 10 patients In addition the data to be utilized in the retrospective aspect of the study contains information on approximately 30 patients and their MRS scans The trends found in this data will be used to guide data analysis for the prospective study Finally given the relative distribution and frequency of histologies seen in the new patient CNS clinic at the CCI the investigators feel the target accrual of 30 patients is feasible within the time restraints of the project
Malignant glioma is the most common primary brain tumor in adults Despite aggressive therapy less than 40 of these patients are expected to live beyond 5 years External beam radiotherapy following maximal surgical resection is the mainstay of treatment for this group of patients Recent intensification of local therapy with focused radiotherapy planning has resulted in successful escalation of dose Further improvement in the therapeutic index of therapy is desirable
Radiologic characterization of glial tumors relies predominantly on CT and MRI images these studies provide good anatomic information regarding the size and location of the tumor as well as surrounding structures but are unable to evaluate viability or proliferative activity of tumors Thus the enhancing lesion on CT or MRI may not correspond precisely to areas of viable tumor especially after surgery and radiotherapy Also because contrast enhanced MRI relies on regions of blood brain barrier BBB breakdown it is not tumor specific thus non-neoplastic processes may lead to findings similar to disease progression This phenomenon can make conventional radiologic follow-up difficult in patients who have received radiotherapy as such imaging techniques are limited in their ability to discern radiotherapy effect and necrosis from recurrence and progression Finally because they do not discriminate viable tumor CT and MRI are of limited usefulness in assessing response to therapy and are unable to effectively predict outcome Magnetic Resonance Spectroscopy MRS is a relatively new technology which may be able to address these issues
The objective of the current study is to investigate the changes that occur in tumor related magnetic resonance MR spectra over the course of radical radiotherapy for malignant glioma The primary endpoint for the study will be to identify characteristic evolving metabolite patterns on MRSI before during and after radiotherapy that correlate with overall survival and progression-free survival in high grade gliomas Secondary endpoints will involve correlation of MRSI metabolite patterns with time to progression and Karnofsky performance status
Eligibility Criteria
Patients must be older than 18 years of age
Patients must have histologically proven malignant glioma of the brain
Patients must have bi-directionally measurable enhancing residual disease by T1 weighted image
Patients must be willing to undergo high dose radiotherapy to the brain for the treatment of their glial tumor
Patients must be willing and able to comply with all study requirements
The patient or legally authorized representative must fully understand all elements of informed consent and sign the consent document
Ineligibility Criteria
Ineligibility criteria include
History of previous RT to the head and neck region
History of lupus scleroderma or RT hypersensitivity
Co-existing medical condition precluding radiotherapy
Psychiatric conditions precluding informed consent
Medical or psychiatric conditions precluding MR studies eg pacemaker aneurysm clips neuro stimulator cochlear implant severe claustrophobiaanxiety
Patients will be approached for study participation at the time of their initial radiation oncology consultation in the outpatient department of the Cross Cancer Institute CCI Patients who wish to participate and satisfy the eligibility and exclusion criteria will be required to review and sign the consent form at that time Patients will then undergo regular staging investigations construction of an immobilizing shell treatment planning MRI and CT simulation These studies are typically completed 2 weeks after the initial consult Radiotherapy will commence approximately 3-4 weeks after the initial consult At week 0 of RT prior to beginning therapy the patient will undergo the baseline MRS The mid-RT MRS study will be performed during week 4 of RT The post therapy scan will take place 2 months post-therapy From then on patients will be seen in clinic every 2-4 months for follow-up and will undergo MRI and MRS scans with each visit for 1 year
Data Collection and Statistical Analysis
The height of each MRS metabolite peak will be measured from voxels within the enhancing MRI lesion and from voxels in normal brain for each patient Relative metabolite values normalized to the value in normal brain will then be generated as well as relative metabolite ratios eg relative cholinerelative NAA for each time point week 0 week 4 and post-RT at follow-up For each patient the relative metabolite levels and ratios will be plotted over time Patients will then be partitioned into groups based on similar evolving MRS pattern For each of the groups curves of survival and disease free progression will be generated by the Kaplan-Meier method The curves will be analyzed for statistical significance by the log-rank method
The investigators plan to accrue 30 patients for the present study They are confident 30 patients will be sufficient to generate statistically significant results In a study of the effects of brain tumor radiotherapy on normal brain as imaged by NMR spectroscopy Urtasun et al were able to find statistically significant metabolite changes on proton MRS images with only 10 patients In addition the data to be utilized in the retrospective aspect of the study contains information on approximately 30 patients and their MRS scans The trends found in this data will be used to guide data analysis for the prospective study Finally given the relative distribution and frequency of histologies seen in the new patient CNS clinic at the CCI the investigators feel the target accrual of 30 patients is feasible within the time restraints of the project
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None