Phase III Trial of Salvage Stereotactic Radiosurgery (SRS) or SRS + Hippocampal-Avoidant Whole Brain Radiotherapy (HA-WBRT) for First or Second Distant Brain Relapse After Upfront SRS With Brain Metastasis Velocity >/= 4 Brain Metastases/Year
This phase III trial compares the effect of adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery versus stereotactic radiosurgery alone in treating patients with cancer that has spread to the brain and come back in other areas of the brain after earlier stereotactic radiosurgery. Hippocampus avoidance during whole-brain radiation therapy decreases the amount of radiation that is delivered to the hippocampus, which is a brain structure that is important for memory. The medicine memantine is also often given with whole brain radiation therapy because it may decrease the risk of side effects of radiation on thinking and memory. Stereotactic radiosurgery delivers a high dose of radiation only to the small areas of cancer in the brain and avoids the surrounding normal brain tissue. Adding whole brain radiotherapy with hippocampal avoidance and memantine to stereotactic radiosurgery may be effective in shrinking or stabilizing cancer that has spread to the brain and returned in other areas of the brain after receiving stereotactic radiosurgery.
• Patients must have developed their first or second distant brain relapse(s) at least 8 weeks after upfront SRS and within 21 days prior to randomization
‣ Distant brain relapse lesions to be treated must measure =\< 3.0 cm in maximal extent and total volume of distant brain relapses to be treated must measure \< 30 mL on the contrast-enhanced diagnostic magnetic resonance imaging (MRI) brain scan obtained within 21 days prior to randomization
⁃ Distant brain relapse lesions must be diagnosed on MRI, which will include the following elements:
• REQUIRED MRI ELEMENTS
‣ Post gadolinium contrast-enhanced T1-weighted three-dimensional (3D) spoiled gradient (SPGR). Acceptable 3D SPGR sequences include magnetization-prepared 3D gradient recalled echo (GRE) rapid gradient echo (MP-RAGE), turbo field echo (TFE) MRI, BRAVO (brain volume imaging) or 3D fast FE (field echo). The T1-weighted 3D scan should use the smallest possible axial slice thickness, not to exceed 1.5 mm
⁃ Pre-contrast T1 weighted imaging (3D imaging sequence strongly encouraged)
⁃ A minimum of one axial T2 fluid attenuated inversion recovery (FLAIR) (preferred) or T2 sequence is required. This can be acquired as a 2D or 3D image. If 2D, the images should be obtained in the axial plane
∙ ADDITIONAL RECOMMENDATIONS
‣ Recommendation is that an axial T2 FLAIR (preferred) sequence be performed instead of a T2 sequence
⁃ Recommendation is that that pre-contrast 3D T1 be performed with the same parameters as the post-contrast 3D T1
⁃ Recommendation is that imaging be performed on a 3 Tesla (3T) MRI
⁃ Recommendation is that the study participants be scanned on the same MRI instrument at each time point
⁃ Recommendation is that if additional sequences are obtained, these should meet the criteria outlined in Kaufmann et al., 2020
⁃ If additional sequences are obtained, total imaging time should not exceed 60 minutes
• Brain metastasis velocity (BMV) since upfront SRS must be \>= 4 brain metastases/year
• The patient or a legally authorized representative must provide study-specific informed consent prior to study entry
• Pathologically (histologically or cytologically) proven diagnosis of non-small cell lung cancer, melanoma, breast cancer, renal cell carcinoma, or gastrointestinal cancer within 10 years prior to randomization. If the original histologic proof of malignancy is greater than 10 years, then pathological (i.e., more recent) confirmation is required (e.g., from a systemic metastasis or brain metastasis)
‣ Other histologies are not permitted
• History and physical examination within 28 days prior to randomization
• Karnofsky performance status of \>= 70 within 28 days prior to randomization
• Calculated creatinine clearance (CrCl) \>= 30 ml/min (within 28 days prior to randomization)
• Blood urea nitrogen (BUN) within 1.5 times the institutional upper limit of normal (ULN) (e.g., if the ULN is 20 mg/dL, then BUN up to 30 mg/dL is permitted) (within 28 days prior to randomization)
• Negative urine or serum pregnancy test (in women of childbearing potential) within 14 days prior to randomization