The Feasibility and Role of Hyperpolarized 13C-Pyruvate MR Spectroscopy in Monitoring Patients With Intracranial Metastasis Treated With Stereotactic Radiosurgery (SRS)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 276
- 试验地点
- 1
- 主要终点
- Is an MRI image produced? Y/N?
研究概览
简要总结
Upwards of 40% of cancer patients will develop brain metastases during their illness, most of which become symptomatic. The burden of brain metastases impacts the quality and length of survival. Thus the management of brain metastases is a significant health care problem. Standard treatment options include stereotactic radiosurgery and/or whole brain radiation. There is a great interest in studying the association between the functional characteristics of tumors - such as tumour hypoxia and lactate accumulation - and clinical outcomes in order to guide management. These characteristics may predict future tumor behavior and stratify risk of therapy failure. Hyperpolarized 13C MR imaging is a novel functional imaging technique that uses 13C-labeled molecules, such as pyruvate, and MRS to image in vivo tissue metabolism.
There is significant clinical heterogeneity in patients with brain metastasis due to differences in underlying tumour biology. Biochemical differences in tumour metabolism have been shown to correlate with response to therapy. While the significance of tissue hypoxia for radiosensitivity has been established for years, the impact of lactate accumulation on radiosensitivity has only recently been recognized. Studies have shown that tissue lactate levels correlate with radioresistance in several human tumours. Hyperpolarized 13C pyruvate MRS has been shown in numerous pre-clinical studies and a recent clinical study to have great potential as a metabolic imaging tool. Our study seeks to establish the role of hyperpolarized 13C MRS in characterizing the metabolic features of intracranial metastasis. The results of this study will provide insight into intracranial metastatic disease signatures with MR spectroscopy and determine if there is added benefit for incorporation of this new technique into future clinical MRI protocols. If the technique can accurately differentiate between aggressive and indolent tumours based on MR spectroscopic patterns, hyperpolarized 13C MRS may have wide-ranging utility in the future. In the era of personalized medicine, the ability of imaging tests to predict response to therapy would open the door for individualized treatment options specific to each patient's disease biology.
详细描述
This is a pilot prospective, single-institution study in both control participants, control participants with mild cognitive impairment and Alzheimer's disease and participants with evidence of intracranial metastases who will be planned for brain radiation therapy. Control participant accrual will be done through advertisements. For control participants with mild cognitive impairment, Alzheimer's disease and intracranial metastatic disease screening and accrual will be completed by a member of the participant's Circle of Care. Clinical procedures will be completed at Sunnybrook Health Sciences Centre (SHSC) by the study's Qualified Investigator or medical designate. Eligible control participants must meet the study's inclusion and exclusion criteria and MRI eligibility. Intracranial metastatic participants must meet the study's inclusion and exclusion criteria, MRI eligibility will be undergoing radiation therapy (stereotactic radiotherapy).
The study will be divided into three parts:
Part I (Controls)
- Population: up to 146 study participants, ≥18 years of age
- Each participant in Groups A to G and J and K will undergo a single MRI sequence with a single hyperpolarized 13C pyruvate injection. Participants in group H, I, and M will undergo MRI sequences with two consecutive injections of hyperpolarized 13C pyruvate. The scans are expected to be of approximately 60 to 75 minutes in length.
Group A: up to 6 participants ≥ 18 years of age. Group B: up to 10 male participants between the age of 18-39 Group C: up to 10 female participants between the age of 18-39 Group D: up to 10 male participants between the age of 40-59 Group E: up to 10 female participants between the age of 40-59 Group F: up to 10 male participants ≥ 60 years of age Group G: up to 10 female participants ≥ 60 years of age Group H: up to 10 male or female participants ≥ 18 years of age Group I: up to 10 male or female participants ≥ 18 years of age Group J: up to 10 male or female participants ≥ 60 years of age with Mild Cognitive Impairment Group K: up to 10 male or female participants ≥ 60 years of age with Alzheimer's disease Group L: up to 10 male or female participants ≥18 years of age Group M: up to 30 male or female participants ≥18 years of age
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Part I (Controls) Group A
- •Participants of all ethnic groups/race categories (≥18yrs old)
- •Informed consent Group B
- •Male participants of all ethnic groups/race categories (between the age of 18-39)
- •Informed consent Group C
- •Female participants of all ethnic groups/race categories (between the age of 18-39)
- •Informed consent Group D
- •Male participants of all ethnic groups/race categories (between the age of 40-59)
- •Informed consent Group E
- •Female participants of all ethnic groups/race categories (between the age of 40-59)
- •Informed consent Group F
- •Male participants of all ethnic groups/race categories (≥60 yrs old)
- •Informed consent Group G
- •Female participants of all ethnic groups/race categories (≥60 yrs old)
- •Informed consent Group H and I
- •Male or female participants of all ethnic groups/race categories (≥18 yrs old)
- •Informed consent Group J
- •Male or female participants of all ethnic groups/race categories (≥60 yrs old)
- •Informed consent
- •Diagnosed with mild cognitive impairment Group K
- •Male or female participants of all ethnic groups/race categories (≥60 yrs old)
- •Informed consent
- •Diagnosed with mild Alzheimer's disease Group L
- •Male or female participants of all ethnic groups/race categories (≥18 years of age)
- •Informed consent Group M
- •Male or female participants of all ethnic groups/race categories (≥18 years of age)
- •Informed consent
- •Part II & III
- •Adult participants of all ethnic groups/race categories (age ≥18 yrs old)
- •Radiographic diagnosis of brain metastases and pathological confirmation of a solid cancer primary
- •Metastatic brain tumor amenable to Stereotactic radiosurgery or radiotherapy
- •Participants on dexamethasone must be on a stable dose at the time of baseline MRI and 1-5 days post-SRS MRI
- •Estimated survival more than 6 months
- •Informed consent
排除标准
- •Prior brain radiotherapy for the specific index or lesion to be imaged in the study
- •For groups B to I, L, and M only: Montreal Cognitive Assessment (MoCA) score <26
- •The participant will also be asked to complete the standard MRI safety screening questionnaire, prior to their research scan and participation in the study.
- •Contraindications to MRI including:
- •Participants weighing >136 kg (weight limit for the scanner tables)
- •Participants with pacemakers, cerebral aneurysm clips, shrapnel injury or implantable electronic devices not compatible with MRI.
- •Claustrophobia to the extent that the participant cannot stay in the MRI for 45-60 minutes
- •Known adverse reactions to the contrast agent Gd-DTPA
- •Inability to lie still for 45-60 minutes
- •Participants with a high risk factor for nephrogenic systemic fibrosis (NFS).
- •Participant declines the procedure or further procedures;
- •Participant is not well enough to undergo MRI scanning;
- •Participant is unable to complete the MRI procedure for any reason or is non-compliant with MRI requirements.
- •For groups J and K, a <1 lacunar infarct or any cortical subcortical infarct or moderate to severe white matter disease
- •For groups J and K, any other structural brain lesion that could affect cognition
研究组 & 干预措施
Intracranial Metastasis Part II
MRI with injection of hyperpolarized 13C pyruvate prior to radiation treatment.
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
Control Participants Part I
A MRI with injection of hyperpolarized 13C pyruvate.
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
Intracranial Metastasis Part III
MRI with injection of hyperpolarized 13C pyruvate prior to radiation treatment. MRI with injection of hyperpolarized 13C pyruvate following radiation treatment.
MRI with injection of hyperpolarized 13C pyruvate following radiation treatment if adverse radiation effect is identified on post-SRS follow-up images.
干预措施: Hyperpolarized 13C-Pyruvate (Drug)
结局指标
主要结局
Is an MRI image produced? Y/N?
时间窗: ~30-60 minutes of MRI time.
To demonstrate the first 13C-metabolic images of the human brain, alone with the required hardware and data acquisition methods.
次要结局
未报告次要终点