Brain Metastasis

Our Specialists for Brain Metastasis

Brain metastases are the most common brain tumors in adults, and how they are treated has changed dramatically. Our neurosurgeons work side-by-side with medical and radiation oncologists to tailor a plan to your specific cancer, your number of lesions, and how you are feeling day-to-day.

Bakhtiar Yamini, M.D.

Vice Chair for Academic Affairs; Director, Neurosurgical Oncology

Dr. Yamini is a brain tumor surgeon and scientist who serves as Vice Chair for Academic Affairs and Director of Neurosurgical Oncology at UChicago. In the operating room, he uses advanced imaging and navigation tools for stereotactic biopsy, laser ablation, and image-guided maximal resection. In his lab, he runs NIH-funded research into why some tumors resist treatment and into biodegradable nanoparticle vectors that deliver drugs directly to CNS tumors. As Director of Neurosurgical Oncology, Dr. Yamini is often the surgeon who resects large or symptomatic brain metastases at UChicago, and his lab's work on NF-kB-driven drug resistance and nanoparticle drug delivery feeds directly into how recurrent metastases are approached. He is also the principal investigator of a multi-institutional phase I trial combining acetazolamide with temozolomide in MGMT-methylated malignant glioma (Neuro-Oncology Advances, 2024).

Peter Christian Warnke, M.D.

Section Chief, Functional Neurosurgery & Epilepsy

Dr. Warnke is an international leader in functional neurosurgery and has performed over 6,000 stereotactic surgeries and more than 3,000 brain tumor surgeries. He is only the second neurosurgeon worldwide to perform laser hemispherotomy, and he has completed over 400 laser ablation surgeries since arriving at UChicago. He is funded by four NIH grants including the BRAIN Initiative, and he directs the NAUTILUS trial for thalamic stimulation in drug-resistant epilepsy. For brain metastases that are deep, recurrent after prior radiation, or too risky for open resection, Dr. Warnke offers MRI-guided laser interstitial thermal therapy (LITT) — a minimally invasive ablation he has performed more than 400 times at UChicago. He also has decades of experience with stereotactic biopsy for lesions where tissue is needed to guide targeted or immunotherapy.

Youssef G. Comair, M.D., FRCSC

Section Chief, Neurosurgical Oncology

Dr. Comair is Section Chief of Neurosurgical Oncology and a pioneer of awake craniotomy for tumors in eloquent cortex. He has authored over 120 peer-reviewed publications and two neurosurgery textbooks, and he founded the first comprehensive epilepsy surgery program in the Middle East and North Africa. He trained at the Montreal Neurological Institute and previously held faculty positions at Cleveland Clinic, UCLA, Johns Hopkins, Baylor, and the American University of Beirut. Dr. Comair, Section Chief of Neurosurgical Oncology, is a pioneer of awake craniotomy and uses intraoperative mapping when a brain metastasis sits near speech, language, or motor areas — the situation where maximal safe resection most depends on surgeon experience. He has authored over 120 peer-reviewed publications and two neurosurgery textbooks on these techniques.

What Is a Brain Metastasis?

A brain metastasis is a tumor in the brain made up of cancer cells that originally came from another organ. The cancer has traveled through the bloodstream — most often from the lung, breast, skin (melanoma), kidney, or gastrointestinal tract — and taken root in the brain tissue. Because the cells still look and behave like the original cancer, a breast cancer that spreads to the brain is treated as breast cancer, not as a new brain tumor.

Brain metastases are by far the most common tumors found inside the adult skull. Roughly 20-40% of patients with advanced cancer will develop at least one brain metastasis at some point, and the number has been rising as newer systemic treatments help people live longer with metastatic disease.

You may have a single brain metastasis or multiple lesions — that distinction matters, because it often changes which treatment is offered first. Twenty years ago, any number of brain metastases typically meant whole-brain radiation and a short prognosis. Today, with focused radiosurgery, better drugs that cross the blood-brain barrier, and immunotherapy, a diagnosis of brain metastasis is a treatable problem rather than an automatic end-stage event.

What Does It Feel Like?

About two-thirds of brain metastases cause symptoms; the rest are found incidentally on a scan done for staging or follow-up. Symptoms depend on where the tumor sits and how much swelling it causes in the surrounding brain.

Common symptoms

• Headaches — often worse in the morning, sometimes with nausea
• New weakness or clumsiness on one side of the body
• Seizures — sometimes the very first sign of a previously unknown brain metastasis
• Trouble with speech, language, or finding words
• Changes in vision, double vision, or loss of part of the visual field
• Memory problems, confusion, or personality changes noticed by family
• Unsteady walking or difficulty with balance

When the lesion is "silent"

Small metastases — especially those picked up on surveillance MRI in patients already known to have cancer — often cause no symptoms at all. That is actually good news: asymptomatic metastases are usually the easiest to treat because they can be targeted with stereotactic radiosurgery before they get big enough to swell the brain or block fluid flow.

How Is It Diagnosed?

The workup usually moves quickly once a brain metastasis is suspected.

MRI with contrast

The most important test is a contrast-enhanced brain MRI. Metastases typically show up as one or more round, enhancing lesions at the junction between gray and white matter, often with a surrounding ring of swelling (edema). MRI is much more sensitive than CT — it can pick up lesions as small as 1-2 mm, which is critical when deciding between single-lesion and multi-lesion treatment plans.

Looking for a primary cancer

If brain lesions are the first sign of cancer (which happens in about 10-15% of cases), your team will search for the primary with a CT of the chest, abdomen, and pelvis, often a PET/CT, and blood work. Lung cancer is the single most common source, followed by breast cancer and melanoma.

Biopsy — when it is needed

If the primary cancer is already known and the MRI looks typical, a biopsy may not be necessary. But when the diagnosis is uncertain, when an MRI lesion could equally be a primary brain tumor or an abscess, or when molecular testing of the brain lesion itself could change therapy, a stereotactic needle biopsy or full surgical resection is performed. Increasingly, the brain lesion is biopsied or resected not just to make a diagnosis but to profile the tumor's mutations — the genetic fingerprint of a brain metastasis can differ from the original primary and reveal targets for newer drugs.

Types of Brain Metastasis

Brain metastases are usually described along two axes: how many there are and whether they are causing symptoms. Both shape the treatment plan.

Single versus multiple metastases

• Single (solitary) metastasis — one visible brain lesion. This is the scenario where surgery has the strongest evidence base, especially if the lesion is large, in an accessible location, or causing symptoms. The landmark Patchell trial showed that patients with a single metastasis live significantly longer when surgery is added to radiation rather than receiving radiation alone.
• Oligometastatic (2-4 lesions) — a small number of lesions, each of which can typically be targeted individually with stereotactic radiosurgery. Surgery is reserved for the largest or most symptomatic one.
• Multiple metastases (5 or more) — historically treated with whole-brain radiation, but large prospective studies (including JLGK0901) have shown that SRS treating up to 10 lesions gives similar survival with much better quality of life. Drug therapy that penetrates the brain is often a bigger part of the plan here.

Symptomatic versus asymptomatic

• Symptomatic lesions — those causing weakness, seizures, or pressure — often need urgent intervention to relieve swelling (with steroids), stop seizures, and remove or shrink the tumor. Surgery is frequently the fastest way to decompress a large, symptomatic lesion.
• Asymptomatic lesions — typically found on surveillance imaging — can usually be treated electively with SRS, often as an outpatient in a single day.

Where the cancer came from matters

Different primary cancers behave differently in the brain and respond to different drugs. HER2-positive breast cancer and EGFR- or ALK-driven lung cancer now have targeted pills that can shrink brain metastases. Melanoma and renal cell cancer often respond to immunotherapy. Your oncology team will tailor systemic therapy to your tumor's molecular profile, not just its location.

How Is It Treated?

There is no single right answer for brain metastases — the best plan weaves together neurosurgery, radiation, and modern drug therapy, chosen for your specific situation. Most patients at UChicago are reviewed in a multidisciplinary tumor board where all three specialties discuss the case together before recommending a plan.

Surgery

Surgery is usually recommended when:

• There is a single large lesion causing symptoms or pressure
• Tissue is needed to confirm a diagnosis or profile the tumor genetically
• A metastasis is blocking spinal fluid and causing hydrocephalus
• A lesion has failed prior radiation and is growing

The landmark Patchell 1990 trial randomized patients with a single brain metastasis to surgery plus whole-brain radiation versus radiation alone. Patients who had surgery lived significantly longer (median 40 weeks vs. 15 weeks), kept their independence longer, and had far fewer local recurrences. That study is the reason surgery is still considered the cornerstone treatment for a single, accessible, symptomatic metastasis.

At UChicago, resections are done with intraoperative neuronavigation, awake mapping when the lesion sits near speech or motor cortex, and high-definition microscopy to remove the whole tumor while protecting critical function.

Stereotactic radiosurgery (SRS / Gamma Knife)

Stereotactic radiosurgery delivers a single, highly focused dose of radiation to a brain metastasis while sparing the surrounding tissue. It is not actually surgery — there is no incision — but it has become the workhorse of brain metastasis care. SRS can now safely treat up to 10 (and sometimes more) lesions in a single session, and local control rates for small-to-moderate metastases exceed 85-90%.

SRS is often used:

• As the first-line treatment for asymptomatic lesions up to about 3 cm
• After surgery to sterilize the resection cavity and lower the chance the tumor comes back at the same spot
• For new lesions that appear on follow-up imaging while the patient is on systemic therapy

Whole-brain radiation (WBRT) — now used selectively

For decades, whole-brain radiation was the default treatment for brain metastases. Today it is used much more sparingly. The reason is that WBRT, while effective at controlling microscopic disease, causes memory and thinking problems in many patients. Trials including Chang 2009, Brown NCCTG N0574, and Brown N107C have shown that using focused SRS instead of WBRT preserves cognition without shortening survival. WBRT still has a role when there are very many small lesions, in some small-cell lung cancer cases, or when leptomeningeal spread is present, and modern hippocampal-avoidance techniques plus memantine help reduce the cognitive cost.

Systemic therapy — targeted drugs and immunotherapy

This is where brain metastasis care has changed the most in the last decade. Newer drugs cross the blood-brain barrier and attack metastases at the molecular level:

• Lung cancer — osimertinib (EGFR-mutant), alectinib and lorlatinib (ALK-rearranged) all have strong brain activity
• Breast cancer — tucatinib and trastuzumab deruxtecan are active against HER2-positive brain metastases
• Melanoma — BRAF/MEK inhibitors and checkpoint immunotherapy (ipilimumab + nivolumab) shrink brain lesions in a substantial number of patients
• Renal cell carcinoma — cabozantinib and checkpoint combinations have activity in the brain

For selected patients, systemic therapy is now being used before or instead of local brain treatment, with local radiation or surgery held in reserve.

Laser ablation (LITT) for recurrent or deep lesions

For lesions that have already been irradiated and are growing again — particularly when it is unclear whether the growth is tumor recurrence or radiation injury — laser interstitial thermal therapy (LITT) is a minimally invasive option. Through a tiny incision, a laser fiber is placed into the lesion under MRI guidance and heats the tumor until it dies. Patients typically go home the next day.

What Are the Outcomes?

Here is the most important thing to understand about prognosis in brain metastasis: how long you live depends much more on your primary cancer and overall health than on the brain lesions themselves. A patient with a single brain metastasis from a slow-growing, targetable lung cancer who still feels well can live several years. A patient with uncontrolled disease elsewhere and poor performance status has a shorter expected survival regardless of how well the brain lesions are treated.

The ds-GPA prognostic index

Oncologists use a validated tool called the Diagnosis-Specific Graded Prognostic Assessment (ds-GPA), developed by Sperduto and colleagues, to estimate survival. The ds-GPA takes into account:

• The type of primary cancer
• Age
• Your performance status (how well you are functioning day-to-day)
• The number of brain metastases
• Whether cancer is active outside the brain
• For some cancers, molecular markers (HER2, EGFR, ALK, BRAF)

Median survival by ds-GPA score ranges from roughly 3 months in the lowest-risk group to more than 4 years in the highest, depending on primary. The table below shows approximate median survival by primary cancer using modern systemic therapy:

Local control is excellent — but the disease is systemic

For the brain itself, modern treatment works remarkably well. Surgery plus SRS to the resection cavity gives local control rates above 80-90% at one year. SRS alone for small lesions achieves similar local control. The challenge is not usually the specific lesion that was treated — it is the appearance of new lesions elsewhere in the brain, which is why close follow-up MRI every 2-3 months is essential.

The bottom line is that brain metastasis is now a chronic problem to be managed, not a terminal event, for many patients. The most important decisions you will make are about the team coordinating your care: a multidisciplinary group that can combine surgery, radiosurgery, and the newest drug therapy will give you the best chance at both surviving longer and living well.

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