Avoiding Radiation Therapy Due to Intracranial Response to Chemotherapy, Targeted Therapy and/or Immuno-ONcology Therapy for Brain Metastases: Pilot Pragmatic Trial

• Pathologically (histologically or cytologically) proven diagnosis of a solid tumor malignancies within 5 years prior to registration. If the original histologic proof of malignancy is greater than 5 years, then more recent pathologic confirmation (e.g., from a systemic site or brain metastasis) or unequivocal imaging confirmation of extracranial metastatic disease (e.g. CT of the chest/abdomen/pelvis, PET/CT, etc.) is required. These scans are considered standard-of-care (SOC) and will not be ordered for research purposes. Initiation or planning for initiation of systemic therapy to include one or more of the following categories expected to cause an intracranial response:
• Brain penetrant targeted therapies (e.g. tyrosine kinase inhibitors, multikinase inhibitors, EGFR inhibitor, ALK inhibitor, BRAF/MEK inhibitor)
• Checkpoint inhibitor immunotherapy (e.g. PDL-1 inhibitors, PD1 inhibitors, CTLA-4 inhibitors)
• HER2 antibody-drug conjugate (e.g. TDM1, TDX-D)
• Anti-Hormone therapies for Breast Cancer
• Cytotoxic chemotherapy alone may be started initially, but with plan for immunotherapy or eligible targeted therapy noted above before the re-evaluation MRI head At least 1 brain metastasis that not planned for radiation therapy or surgery. All brain metastases not planned for resection much be ≤3 cm, with no minimum size required. Systemic therapy has started within 4 weeks of MRI brain showing new or progressive disease or plan to start systemic therapy within 4 weeks of MRI brain showing new or progressive disease. Ability to obtain MRI head scans with contrast. All MRI head scans must have slice thickness ≤1.5 mm. Age ≥ 18 years KPS \>60 Ability to understand and the willingness to sign a written informed consent.

No use of the planned new systemic therapy meeting 2.1.2 criteria to address brain metastases within the last 6 months. Prior radiotherapy to the active brain metastases (partial or whole brain irradiation, or prophylactic cranial irradiation \[PCI\]) Patients pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants. Negative urine pregnancy test (in persons of childbearing potential) within 14 days prior to registration. Childbearing potential is defined as any person who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or who is not postmenopausal. Serious medical comorbidities that in the opinion of the investigator would prevent participation in this study. Known leptomeningeal disease (LMD) \-