Stereotactic Radiation for Growing/Changing Brain Metastases With Same-Day Radiation Planning and Treatment With Margin Reduction

A Double-Blind Phase II Randomized Study of Adaptively Delivered LINAC-Based Stereotactic Radiation for Volatile Brain Metastases With Same-Day Planning and Margin Reduction

The goal of this study is to evaluate the feasibility and effectiveness of same-day radiation planning and treatment. The study will shorten the time interval between radiation planning (radiation mapping) and radiation treatment. The intent of this shorter time interval is to increase the likelihood that the brain metastases being treated remain fully within the high-dose radiation fields.

Participants will be randomized to receive brain-directed stereotactic radiation with a 1mm margin or 0mm margin, have their simulation/radiation planning imaging on the same day that brain-directed stereotactic radiation is delivered, and have repeat simulation/radiation planning scans during the course of treatment if more than 2-3 days have elapsed since the most recent scans.

Adaptively designed radiation, which adjusts a given radiation plan for real time changes in patient position or anatomy, has become a standard approach within many oncologic entities to combat the effect of shifts between simulation and treatment. Adaptively planned SRS/SRT with same day brain MRI and treatment delivery offers potential to quantify the impact of treatment planning time while also reducing margins and potentially improving rates of local recurrence and radiation necrosis. This trial aims to explore the viability of adaptively designed SRS/SRT with same day planning and treatment in combination with tighter planning margins in both controlling brain metastases locally and minimizing the risk of radiation necrosis in a phase 2 randomized study.

Participants will have a preliminary stereotactic treatment plan created from a diagnostic brain MRI indicating the need for treatment. The preliminary plan will undergo departmental-standard physics, therapy, and quality assurance checks, spanning a total of 1-2 weeks, after which the patient will return for treatment. On the day of treatment (SRS) or start of treatment (SRT), a repeat MRI brain will be performed for planning purposes on an MRI simulator. A synthetic computed tomography (CT) scan will be generated from the new MRI. The previously generated contours and plan will be adapted to the new MRI and the fused synthetic CT. Lastly, the treatment will be delivered.

The primary objective is to assess the percentage of patients that demonstrate tumor beyond the standard planning margin (1.0mm PTV) at the time of stereotactic treatment.

An important secondary objective is to quantify local recurrence and radiation necrosis rates in patients treated with same day simulation and treatment, based on randomization to a PTV of 0mm or 1.0mm.

Inclusion Criteria:

1. Participants must have a biopsy proven solid malignancy with at least one intact, residual or recurrent, intracranial lesion radiographically consistent with or pathologically proven to be a brain metastasis meeting one of the following criteria:

   1. Growth of 1.0mm per week or more, on average, based on the two most recent brain MRIs preceding study enrollment
   2. Abutment, to within 1.0cm, of a region of intracranial edema
   3. Proximity (within 5.0cm) to a surgical cavity created within 30 days of enrollment
   4. Proximity (within 5.0cm) to another source of physical displacement

2. Age of at least 18 years

3. Karnofsky performance status of at least 60

4. Estimated survival of at least 3-6 months in the opinion of the enrolling clinician and/or study PI

5. Ability to understand and the willingness to sign a written informed consent document by either ink on paper or a DF/HCC approved eConsent medium

Exclusion Criteria:

1. Participants who cannot tolerate a brain MRI
2. Patients who cannot receive gadolinium
3. Participants with end stage renal disease
4. Participants with widespread, definitive leptomeningeal disease
5. Pregnant women are excluded from this study because of the potential deleterious effects of gadolinium on the developing fetus. Because there is an unknown but potential risk for adverse events in nursing infants, women who are breastfeeding are not eligible for this study as well