A Rare Case of Glioblastoma With Extensive Liver Metastases

What To Know About Lung Cancer That Has Spread To The Brain

How Brain Metastases From Lung Cancer Are Treated

If diagnosed and treated early, brain metastases usually respond to therapy. Your treatment plan will depend on your tumors (size, number, location in the brain, and genetic characteristics); the extent of disease outside the brain; and your overall health. Treatment may include:

Surgery Surgery may be an option for people with only one or two brain metastases that are easy to access and remove. It may also work for people who have a larger tumor that's causing compressive symptoms, and removing even a portion of the tumor may help alleviate symptoms. According to a review, surgery is commonly followed by radiation therapy.

Radiation This therapy uses X-rays or other high-energy beams to kill cancer cells. Different methods of radiation are used to treat brain metastases.

People who have smaller brain tumors or tumors that are not surgically accessible or are too advanced for neurosurgery may be good candidates for stereotactic radiosurgery, in which MRIs, CT scans, and computer guidance are used to deliver large doses of radiation directly to tumors.

[5] "This approach can effectively treat metastases with little radiation exposure to other parts of the brain and with minimal side effects," says Dr. Goldman.

If you have many tumors throughout your brain or a large tumor deep in the brain, your doctor may recommend whole-brain radiation, in which radiation is applied to the entire brain to kill tumor cells.

[6] "This method," Goldman explains, "treats the whole area but, unfortunately, comes with more side effects, such as headache, fatigue, nausea, hair loss, and some slowed cognition."

Systemic Therapy With systemic therapies, including chemotherapy, immunotherapy, and targeted therapy, drugs travel through the bloodstream to reach cancer cells throughout the body.

Because many chemotherapy drugs are unable to cross the blood-brain barrier — a network of capillaries that keeps certain substances from reaching the brain — targeted therapy is the primary form used to treat brain metastases, according to a journal article.

[7]

Targeted therapies can identify and attack specific cancer cells with minimal harm to normal cells. For people with lung cancer cells that have specific mutations (such as EGFR and ALK), these therapies can be highly effective.

But if your lung cancer doesn't carry these specific mutations or has spread elsewhere in the body, your doctor may consider other systemic therapies, such as immunotherapy (which uses medicine to activate your own immune system to recognize and kill cancer cells) or chemotherapy.

Palliative Care This type of specialized medical care can include pain management, mental health counseling, spiritual support, and stress management techniques. It's a key component of treatment for patients with metastatic NSCLC.

[8]

Palliative care can help mitigate the side effects of both the cancer and its treatment and significantly improve quality of life. Information and support are available for people with lung cancer and their families at Go2 for Lung Cancer, the American Cancer Society, and the Global Resource for Advancing Cancer Education (GRACE).

Looking Ahead: After Brain Metastases Treatment

After radiation, surgery, or systemic treatment for brain metastases, your doctor will most likely order an MRI to determine how much of the tumor is gone and then follow up with MRIs every few months.

The prognosis for people with NSCLC that's metastasized to the brain is highly variable, so it's important to keep in mind that statistics don't necessarily pertain to your situation. While the outlook was traditionally poor for people with NSCLC and brain metastases, advancements in treatment are continually improving survival rates.

Clinical trials are regularly being conducted to find ways to improve treatment for people with NSCLC that's metastasized to the brain. Ask your doctor whether you may be a candidate for such a trial. You can also search for a clinical trial in your area at ClinicalTrials.Gov.

"Brain metastasis has traditionally been an area that was difficult to study," Goldman says. "But, thankfully, more and more studies are focused on exactly this problem."

Additional reporting by Erica Patino.

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Early Promise For PI3K Inhibitor In Brain Metastases

HOUSTON -- Two-thirds of patients with PI3K-mutant brain metastases responded to the maximum tolerated dose (MTD) of the small-molecule inhibitor paxalisib plus radiation therapy (RT), a small phase I study showed.

Eight of 12 evaluable patients had intracranial responses (all partial) to the dual-modality treatment, supporting the hypothesis that targeted PI3K inhibition has synergy with brain RT in tumors that are often resistant to radiation. The remaining four patients had stable disease, reported Brandon Imber, MD, of Memorial Sloan Kettering Cancer Center in New York City, at the Society for NeuroOncology annual meeting.

"Concurrent daily administration of paxalisib with brain radiotherapy is safe and well tolerated at a maximum dose of 45 mg per day in advanced solid-tumor patients with brain metastases and PI3K pathway mutations," he said. "The results established proof-of-principle for molecularly selected, rational combination studies in radiation oncology to assess safety and ultimately efficacy."

By way of background, Imber noted that partial or whole-brain RT remains standard of care for brain metastases and leptomeningeal carcinomatosis. PI3K-mutated metastases have an increased likelihood of local failure with RT. He and his colleagues hypothesized that combining paxalisib, a brain-penetrant PI3K/mTOR inhibitor, with RT might improve outcomes in patients with PI3K-mutant brain metastases.

The investigators in this dose-escalation study enrolled a total of 21 patients, 17 of whom were evaluable for safety and 12 treated with the MTD of 45 mg/day. Two of the 17 patients had dose-limiting toxicities at the 60-mg dose of paxalisib. Overall, five patients had grade 1 adverse events, four had grade 2 events, and two had grade 3 events (hyperglycemia and nausea).

Imber said future studies should include validation of circulating tumor DNA for patient enrollment and post-treatment monitoring, a longer duration of PI3K inhibition, and the evaluation of neoadjuvant, adjuvant, and maintenance therapy, including use of complementary systemic agents.

Promising Results With TTFields in Glioblastoma

Glioblastoma progression slowed substantially with the addition of tumor treating fields (TTFields) to radiation and temozolomide, and TTFields was associated with a median survival improvement of almost 9 months, a randomized trial showed.

Median progression-free survival (PFS) improved significantly, from 5.6 months with radiation and temozolomide to 9.9 months with the addition of TTFields, representing a 47% reduction in the hazard for disease progression or death with the electric-field therapy (P=0.049). Median overall survival (OS) numerically increased from 17 months to 25.9 months when patients received TTFields plus standard treatment (P=0.515).

"This study demonstrated promising initial outcomes for TTFields therapy as first-line treatment concomitant with chemoradiation," said Rachel Grossman, MD, of Rambam Health Care Campus in Haifa, Israel. "The ongoing phase III TRIDENT trial will provide more robust information about the effects of TTFields therapy when provided with chemoradiation."

TTFields therapy employs low-energy electrical fields to produce an anti-mitotic effect in cancer cells. The currently available devices have approved indications in glioblastoma, mesothelioma, and non-small cell lung cancer.

Grossman reported findings from a randomized trial comparing temozolomide and RT with or without TTFields in patients with newly diagnosed glioblastoma. The primary endpoint was 12-month PFS, and secondary endpoints included OS and median PFS. The study involved 46 patients who had a median age of 62.

The addition of TTFields to upfront therapy resulted in a 1-year PFS rate of 36% versus 19% for the control group (P=0.1) and 2-year PFS rates of 21% and 5% (P=0.07).

Median OS favored the TTFields group, but the difference was not significant (HR 0.80, 95% CI 0.413-1.558). Patients who had at least 75% usage of TTFields had a 2-year OS of 78% versus 34% for the control arm (P=0.01).

Adverse events were primarily dermatologic, consistent with previous experience with the transdermally administered therapy.

Proton Irradiation for Leptomeningeal Disease

The potential role of proton craniospinal irradiation (CSI) for leptomeningeal metastases continues to evolve, a small retrospective analysis suggested.

Patients who received the treatment had a median OS of 13.7 months and a median PFS of 6.5 months. The overall results were driven by those in breast and lung cancer metastases, as patients with other types of leptomeningeal metastases had a median OS of 3.9 months, reported Keng Lam, MD, of City of Hope in Duarte, California.

The results were consistent with those of a small randomized phase II study that showed a median OS of 9.9 months and median PFS of 7.5 months in patients with leptomeningeal metastases treated with proton CSI. The outcomes were significantly better than results with standard photon involved-field radiotherapy.

"Further study is indicated to determine the optimal candidates for photon craniospinal irradiation, sequencing of photon craniospinal irradiation, and choice of sequential therapies," said Lam, who was at the University of Texas MD Anderson Cancer Center in Houston during the study period (December 2020 to January 2024).

The retrospective analysis included 45 patients who completed proton CSI for leptomeningeal disease confirmed by imaging and/or cerebrospinal fluid cytology. The most common primary tumor sites were breast (53%) and lung (20%). About half the patients had active metastasis at diagnosis, and 80% were symptomatic, most commonly headache (31%), cranial neuropathy (31%), and limb weakness/numbness (16%).

Toxicity was predominantly grade 1/2, said Lam. The most common radiation-related side effects were nausea (76%), headache (51%), and fatigue (31%).

Charles Bankhead is senior editor for oncology and also covers urology, dermatology, and ophthalmology. He joined MedPage Today in 2007. Follow

Disclosures

The paxalisib study was supported by Kazia Therapeutics.

Imber disclosed relationships with AstraZeneca, Bayer, GT Medical Technologies, Kazia Therapeutics, and Novartis.

The TTFields study was supported by Novocure.

Grossman reported no conflicts of interest.

Lam reported no relevant relationships with industry.

Primary Source

Society for NeuroOncology

Source Reference: Imber B, et al "Multi-center phase I study of concurrent paxalisib and radiation therapy in patients with solid tumor brain metastases or leptomeningeal metastases harboring PI3K pathway alterations" SNO 2024; Abstract CTNI 43.

Secondary Source

Society for NeuroOncology

Source Reference: Grossman R, et al "Chemoradiation +/- TTFields, followed by maintenance TTFields/TMZ, in newly diagnosed glioblastoma. Results of a single-institution, randomized, phase II clinical study" SNO 2024; Abstract CTNI-25.

Additional Source

Society for NeuroOncology

Source Reference: Lam K, et al "Proton craniospinal irradiation for treatment of leptomeningeal metastasis in patients with solid malignancy: the MD Anderson Cancer Center experience" SNO 2024; Abstract RADT-14.

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