A group of physicians from NewYork-Presbyterian/Weill Cornell Medicine has developed an algorithm for the management of newly diagnosed brain metastases that applies available evidence and the latest advances within a multidisciplinary framework.
Too often, patients with multiple brain metastasis are automatically referred for whole brain radiation therapy, an approach that carries significant adverse effects. This new algorithm offers an individualized approach that accounts not just for the number of metastases but also the patient’s symptoms, the availability of targeted therapies, and the feasibility of radiosurgery, among other factors. The algorithm was developed to reflect the approach employed by the Weill Cornell Medicine Brain Metastasis Tumor Board.
“This idea of individualized, personalized care to help people in both their quality and quantity of life is central. We bring a multidisciplinary framework to every single patient that walks in our door for brain metastasis care,” says Rohan Ramakrishna, MD, Co-Director of the Brain Metastases Program at NewYork-Presbyterian/Weill Cornell Medicine, Chief of Neurological Surgery at NewYork-Presbyterian Brooklyn Methodist, and senior author of the new brain metastases algorithm and editor of the widely cited textbook Central Nervous System Metastases published by Springer in 2020.
The algorithm was published in Neuro-Oncology Advances and outlines various clinical decision-making pathways. For instance, for a patient who presents with metastases of less than 2 cm, is asymptomatic, and is eligible for a systemic therapy that penetrates the central nervous system (CNS), the algorithm suggests a trial of first-line systemic therapy. Toward the other end of the spectrum, for patient with more than 10 metastases and a Karnofsky performance status (KPS) of greater than 70, the algorithm suggests resection of the dominant metastasis (if large, edematous, and/or symptomatic) plus postoperative radiosurgery therapy to the resection bed and stereotactic radiosurgery to at-risk metastases.
While the algorithm indicates that there are still some cases that warrant consideration of whole brain radiation therapy, such as in patients with more than 10 metastases and a poor prognosis, it generally favors the use of stereotactic radiosurgery in the treatment of multiple intracranial metastases.
“There’s widespread acceptance that whole brain therapy will cause neurocognitive deficits. The controversial thing is if someone comes in with 50 metastases, what should we do in that situation?” says Dr. Ramakrishna. “The default in many situations is whole brain radiation therapy, but what we’re trying to argue is, let’s not be reflexive when it comes to those kinds of situations. Let’s think about it thoughtfully and on a case-by-case basis especially with the pipeline of targeted therapies that are being approved for use in patients.”
The default in many situations is whole brain radiation therapy, but what we’re trying to argue is, let’s not be reflexive when it comes to those kinds of situations.
— Dr. Rohan Ramakrishna
Minimizing Radiation in Favor of Surgical Resection and Targeted Therapy
Overall, the algorithm emphasizes the use of surgical resection and targeted therapy, when appropriate, and aims to minimize the use of radiation only to symptomatic lesions and those lesions considered “at-risk” based on current size, future growth, and the presence of edema in patients with numerous metastatic deposits.
The article also reviews the available evidence on treatment based on the number of metastases, as well as how to incorporate systemic therapy.
“There is a lot of data for how we treat a solitary metastasis, how we treat metastases that are four or less, or even 10 or less. But once we get to 10 or more, the evidence starts getting a little bit more murky and more controversial,” says Dr. Ramakrishna. “By laying out what to do in each of those situations, based on the number of metastases first, but then also on the situation you find yourself in within those different groups, we hope to guide clinicians on what to do for the patient.”
The number of brain metastasis is just one factor in determining treatment, according to the approach in the algorithm.
One misconception about brain metastasis care is that performance status should dictate the type of therapy given, limiting a more aggressive approach. In the paper, Dr. Ramakrishna and his colleagues explore the concept of a CNS-specific performance status. Using that approach, a clinician may consider removing or treating a brain metastasis that is causing a deterioration in the patient’s functional status with the expectation that their function will improve after treatment.
“The effect of the brain metastasis on someone’s function, and whether that functional deficit can be reversed by treating that brain metastasis, is a really important consideration,” says Dr. Ramakrishna.
The effect of the brain metastasis on someone’s function, and whether that functional deficit can be reversed by treating that brain metastasis, is a really important consideration.
— Dr. Rohan Ramakrishna
The aim of the team that developed the algorithm was to make it user-friendly and accessible outside of NewYork-Presbyterian/Weill Cornell Medicine. “It was meant to be something that is useful for anybody who wants to be forward-thinking and holisitic in brain metastases care,” says Dr. Ramakrishna.
Multidisciplinary Approach to Brain Metastases
However, he cautioned that modern brain metastases care is not a solo pursuit. “You need a multidisciplinary team. Any center that wants to think about doing this, you need at minimum a neurosurgeon, a radiation oncologist, a neuroradiologist, and a medical oncologist who preferably is subspecialized within their discipline,” says Dr. Ramakrishna. “That really allows you to bring the best thinking for each patient.” Dr. Ramakrishna co-leads the Brain Metastases Center with Kathryn Beal, MD, a NewYork-Presbyterian/Weill Cornell Medicine radiation oncologist.
You need a multidisciplinary team. Any center that wants to think about doing this, you need at minimum a neurosurgeon, a radiation oncologist, a neuroradiologist, and a medical oncologist who preferably is subspecialized within their discipline. That really allows you to bring the best thinking for each patient.
— Dr. Rohan Ramakrishna
The algorithm will likely need to be updated as new therapies and technologies emerge, and Dr. Ramakrishna and his colleagues are also interested in publishing an algorithm on the management of recurrent brain metastases. In the meantime, the multidisciplinary team at NewYork-Presbyterian/Weill Cornell Medicine is exploring how to use focused ultrasound for patients with recurrent brain metastases for whom radiation therapy may no longer be an option.
“One of the problems with radiation therapy is that each time you do it, if it’s the same spot, you get more and more side effects like radiation necrosis. Focused ultrasound works not by radiation, but by heat,” says Dr. Ramakrishna. “The question is, can we ablate areas of recurrent metastases using focused ultrasound technology? That’s a protocol we’re hoping to develop over the next year.”
