Brain Metastasis Velocity (BMV) Model

Why did you develop the Brain Metastasis Velocity (BMV) Model? Was there a particular clinical experience or patient encounter that inspired you to create this tool for clinicians

Stereotactic radiosurgery (SRS) is a focused approach of delivering high dose radiation therapy directly to brain tumors while sparing the surrounding normal brain tissue. This leads to very few side effects, and SRS is typically a one-day procedure. Such a targeted approach is used when the risk of microscopic disease elsewhere in the brain is felt to be low.

There is debate over which patients are most appropriate for SRS in the upfront setting. Generally, patients who present with more than four brain metastases are felt to have a higher risk of developing distant brain failures after SRS.

The alternative to SRS in such cases is whole brain radiation therapy (WBRT), which exposes the entire brain to an effective radiation dose that can treat any tumors observed on imaging, as well as microscopic non-visible disease. By exposing more normal brain tissue to radiation however, WBRT is associated with substantially more neurocognitive toxicity than SRS. Furthermore, WBRT is delivered over 10 separate treatments and requires patients to come in for treatments over the course of 2 weeks.

When patients experience a distant brain failure (i.e., develop new metastases) after initial SRS, it can be difficult to determine if they should receive salvage WBRT or additional SRS. While salvage WBRT does come with more toxicity, the indiscriminate use of SRS is costly and would not help clear potential microscopic disease. The number of metastases at time of failure as well as the time required to develop these new metastases can help us predict which patients are most likely to fail again quickly and who should receive WBRT rather than additional SRS.

What pearls, pitfalls and/or tips do you have for users of the Brain Metastasis Velocity (BMV) Model? Do you know of cases when it has been applied, interpreted, or used inappropriately

The BMV is easy to calculate and can be useful in clinical decision making, but it should not be the sole guide in selecting the most appropriate treatment. As evaluated in our initial publication (Farris 2017), tumor histology and extracranial control should also play a role in the ultimate decision to offer WBRT or SRS after distant brain failure.

For example, patients with melanoma histology were more likely to have a higher BMV and more likely to suffer neurologic death than patients with non-melanoma histologies. On the other hand, patients with HER2 positive breast cancer were more likely to have lower BMV values, and this was probably due to the fact that they were able to achieve better systemic control with targeted agents. In the future, further analyses may be able to help us fine-tune BMV calculations with nomograms based on histology as well as systemic disease status.

What recommendations do you have for doctors once they have applied the Brain Metastasis Velocity (BMV) Model? Are there any adjustments or updates you would make to the score based on new data or practice changes?

Newer targeted agents or immunotherapy agents that have some CNS penetration should also be considered as these will likely impact expected failure patterns. These topics should be explored as the data continues to mature.

In the setting of EGFR positive non-small cell lung cancer, for example, the relatively new targeted agent osimertinib has brain penetration. When these patients present with brain metastases, it is becoming a somewhat controversial subject if clinicians should delay brain radiation in favor of osimertinib alone, or treat with radiation upfront. This should be studied in a prospective fashion.

How do you use the Brain Metastasis Velocity (BMV) Model in your own clinical practice? Can you give an example of a scenario in which you use it?

A patient who experiences a failure with five new brain metastases at one month after their first SRS procedure has a very high velocity and is likely to continue experiencing distant brain failures if treated with additional SRS alone. These patients would likely be best treated with WBRT. On the other hand, a patient who experienced a failure with two new brain metastases at one year after SRS may be a more suitable candidate for additional SRS and could potentially avoid the toxicities of WBRT.

The purpose of the brain metastasis velocity (BMV) is to serve as a clinical guide in the setting of distant brain failure following initial SRS to determine which patients are best suited for salvage WBRT vs additional SRS. It can be calculated quickly at the time of each brain failure.

Any other research in the pipeline that you’re particularly excited about?

The role of upfront SRS is constantly evolving, and this very recent publication by Hughes et al (2019) provides evidence that initial SRS may be appropriate in patients with 5-15 brain metastases.

Michael Farris, MD, is a radiation oncologist at the Wake Forest School of Medicine in North Carolina. Dr. Farris’ primary research is focused on lung cancer as well as stereotactic radiosurgery for brain metastases.