CBF and NCF Changes With Brain Radiation

Inclusion criteria

• Patients with brain metastases will be included in this study. Patients with known malignancies but without brain metastases, or patients with primary brain tumors are not eligible for enrollment.
• MRI confirmed 1-10 lesions. Each lesion must not be intended for resection.
• No prior radiation therapy for brain tumours.
• For patients enrolled to arm B, ability to tolerate RespirAct. Based on studies in patients with severe cerebrovascular disease, an 8 - 16% drop-out rate at the time of the first exposure to RespirAct CVR testing is expected [9]. The fourth generation of this device has been associated with increased tolerability secondary to elimination of a physical rebreathing circuit replaced by a digital re-breath analog. This improvement is expected to achieve a drop-out rate significantly below 10%.
• Patients must have a GPA greater than or equal to 1.0.
• Patients must be able to provide informed consent. Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements. Each patient must sign a consent form prior to enrollment in the trial to document their willingness to participate.
• Patients must have sufficient fluency in English and sufficient motor and visual functioning (corrected or assisted as required) to complete the NCF-A battery.
• Patients must be accessible for treatment, AE assessment and follow- up.
• Limit to KPS ≥ 70 for patients in arm B; no limit for arm A
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive. Women of childbearing potential will have a pregnancy test to determine eligibility.

Exclusion criteria

• Treatment plan respecting normal tissue tolerances using dose fractionation specified within the protocol cannot be achieved.
• Pregnant patients will be excluded from this study.
• Prior cranial radiotherapy
• Inability to complete MRI with contrast of the head, or a known allergy to gadolinium
• Metastatic germ cell tumor, small cell carcinoma, or lymphoma or any primary brain tumor.
• Patients with known malignancies but without brain metastases.
• Image Findings

• Widespread definitive leptomeningeal metastasis
• A brain metastasis that is located ≤ 2 mm of the optic chiasm
• Evidence of midline shift
• Fourth ventricular narrowing, concerning for hydrocephalus
• Patients who have undergone surgical resection of brain tumor are not eligible for enrollment.