Nduka Amankulor, MD, a neurosurgeon and neuro-oncologist at UPMC Hillman Cancer Center and assistant professor of neurological surgery at University of Pittsburgh School of Medicine.
CANCER
Published Date: October 1, 2019
Publication: Bottom Line Health
CANCER
When Cancer Spreads to the Brain: New Treatments Offer Hope
When melanoma or some other cancer spreads to the brain, the prognosis used to be grim. Now, treatment advances are dramatically improving outcomes…
An astounding 20% to 30% of people with cancer develop metastatic brain cancer (MBC)—cancer that has spread from another organ to the brain.
Breast cancer, lung cancer, kidney cancer and melanoma are the main types of cancer that invade the brain. But almost any cancer can produce brain metastases, with an estimated 170,000 new cases every year.
Until recently, the prognosis for people with MBC was grim—only 8% of patients were alive two years after diagnosis, and 2% after five years. But those sad statistics are changing.
Now: The treatment of MBC is being revolutionized by targeted drug therapies that attack genetic mutations driving cancer…immunotherapies that stimulate the body’s own immune system to fight cancer…and precisely focused radiation.
Immunotherapy more than doubled the average survival time of melanoma patients with MBC—from 5.2 months to 12.4 months, according to a study published in Cancer Immunology Research. The effects are even better for melanoma patients with MBC but no other metastases—research found that those who received immunotherapy had an average survival rate of 56 months, compared with 7.7 months for those receiving standard treatment, such as chemotherapy. In other words, MBC patients treated with immunotherapy lived about seven times longer!
What cancer patients and their families need to know…
Early Detection
Many oncologists don’t recommend screening for brain metastases, except for certain tumor types that have a significant predilection for spreading to the brain. Of course, if the patient develops neurological symptoms, such as headaches, numbness, blurred vision, balance difficulties, cognitive decline and/or seizures, then brain screening for a brain tumor is recommended, regardless of the type of cancer.
New thinking: Early detection can extend survival time in patients without neurological symptoms who are at high risk of developing MBC.
My advice for who should get screened…
• Any patient with a new diagnosis of stage II to stage IV lung cancer, whether it’s non-small cell (the most common type) or small cell.
• A melanoma patient with metastatic disease elsewhere in the body—because two out of three of these patients will also develop MBC.
• A breast cancer patient who is positive for HER2 (a gene that plays a role in the development of breast cancer)…or whose tumor lacks hormone receptors (estrogen and progesterone receptors)…or lacks any markers at all (triple-negative breast cancer). The rate of MBC is significantly higher (10% to 15%) in all these breast cancer patients.
The gold standard for early detection is a brain MRI with contrast dye, which can detect brain tumors as small as 2 millimeters in diameter (less than one-tenth of an inch). Especially in patients who are at high risk of developing MBC, insurance may cover the MRI even if there are no neurological symptoms, but be sure to check first. Once MBC is diagnosed, MRIs are obtained roughly every two to four months.
Targeted Therapies
Targeted therapies are drugs (oral or IV) that block or alter specific genes and/or proteins that drive cancer. There have been dozens of clinical trials of targeted therapy in patients with brain metastases—with some remarkable results. For example…
Researchers from the MD Anderson Cancer Center at University of Texas studied melanoma patients with MBC who had the BRAF mutation, which occurs in about half of patients with this disease. The patients received two drugs—dabrafenib (Tafinlar), which targets BRAF…and trametinib (Mekinist), which targets MEK, a mutation similar to BRAF. In a group of 76 patients with BRAF who had never been treated for MBC and whose neurological symptoms were under control, 58% had significant shrinking of their brain tumors—and in four patients the tumors vanished, according to the research, which was published in The Lancet Oncology. The response lasted, on average, six to seven months.
Immunotherapy
Immunotherapy drugs are a class of drugs that stimulate a patient’s immune system, essentially calling it into action. The most widely used immunotherapies are drugs that block checkpoint proteins, such as PD-1 or PD-L1, which suppress inflammatory responses in the immune system.
Scientific evidence: Impressive results with combined drug therapy—ipilimumab (Yervoy) and nivolumab (Opdivo)—were cited in a study published in The New England Journal of Medicine. In that research, when 94 melanoma patients with MBC took both drugs, 81% were alive after one year and 70% after two years—a dramatic increase over the typical survival rate of four to five months before the introduction of immunotherapy.
Focused Radiation
In the past, the standard radiation treatment for MBC was whole-brain radiation—multiple treatments of the entire brain with low-dose radiation.
However, whole-brain radiation has significant side effects, such as a marked decrease in memory and other cognitive abilities. Doctors are now using highly focused radiation therapies called stereotactic radiosurgery. Employing a flexible robotic arm to deliver radiation (CyberKnife), or using a helmet with built-in radiation sources (Gamma Knife), this treatment delivers less total radiation…faster…and more accurately. And its cancer-killing efficacy is as good as whole-brain radiation —with less severe side effects.
Your Plan of Action
To take advantage of the breakthrough treatments for MBC, you need a plan of action. Here are four steps to follow…
STEP #1: Treat the primary cancer. The key in treating cancer is always minimizing your overall cancer burden using the full range of treatments available—such as chemotherapy, radiation, surgery, targeted therapies and immunotherapy. Controlling the primary malignancy reduces the risk of the cancer spreading to the brain.
STEP #2: Ask your oncologist, “Has my tumor been sufficiently molecularly characterized?” Sophisticated genetic tests will show if you’re a candidate for targeted therapy or immunotherapy.
For example, if such testing shows that you have the ALK mutation, treatments for the primary tumor may include targeted therapies such as alectinib (Alecensa), brigatinib (Alunbrig) or lorlatinib (Lorbrena)—all of which also help prevent and/or treat brain metastases.
If a tumor biopsy shows that you have high levels of PD-1 or PD-L1, then you may be a candidate for an immunotherapy drug such as pembrolizumab (Keytruda), nivolumab (Opdivo) or atezolizumab (Tecentriq).
STEP #3: Ask your oncologist, “Are there effective therapies that treat the molecular pathways affecting my cancer—and should we use those therapies to treat my brain cancer?” Once your tumor has been tested for molecular mutations, talk with your oncologist about the targeted and immunological therapies available to treat those problems. You and your doctor should develop a complete list of the targeted therapies and immunotherapies (see examples above) that may be right for you—and then decide which to use.
STEP #4: Demand a multidisciplinary team approach. The best treatment for primary cancer and for MBC is a team approach, typically involving a medical oncologist, a radiation oncologist and a cancer surgeon. The best treatment decisions are made when the entire team talks to one another, face-to-face. This type of multidisciplinary approach is typical of cancer centers that are designated by the National Cancer Institute for offering cutting-edge treatments. To find such an NCI-designated cancer center near you, go to: Cancer.gov/research/nci-role/cancer-centers/find.
