Dr Manmeet Ahluwalia on the Precision Oncology Revolution in Brain Metastases

For decades, a diagnosis of brain metastases was often viewed as a final, daunting chapter in a patient's cancer journey. However, according to Manmeet Ahluwalia, MD, chief scientific officer and chief of Medical Oncology at Baptist Health Miami Cancer Institute, the narrative is shifting rapidly. Through the lens of precision oncology and multidisciplinary care, what was once a prognosis measured in months is now being measured in years.

In a recent discussion with Targeted Oncology, Ahluwalia, who also serves as the Fernandez Family Endowed Chair in Cancer Research, shared his insights into the evolving landscape of brain metastases, particularly those originating from lung cancer.

The Scale of the Challenge

While often discussed as a secondary complication, the sheer volume of brain metastases cases makes it a primary concern for the oncology community. Ahluwalia emphasized that this is not a niche issue.

"Brain metastases are a common clinical problem we encounter in the United States every year," Ahluwalia explained. "100,000 to 200,000 patients are diagnosed with brain metastases every year in the United States. This is as common as, say, a breast cancer or lung cancer."

He noted that while many cancers can spread to the brain, 3 specific culprits lead the pack: lung cancer, breast cancer, and melanoma.¹Among these, lung cancer stands out, with 40% to 50% of patients with lung cancer developing brain metastases.²

Lung Cancer: The "Poster Child" for Precision Medicine

The treatment of lung cancer has undergone a radical transformation, moving away from a one-size-fits-all chemotherapy approach toward highly specific, targeted interventions. This progress is now being felt in the management of brain metastases.

"Lung has really become a poster child for drug development and precision oncology," said Ahluwalia. He noted that the medical community now categorizes these patients into 2 broad clinical groups:

1. Oncogenic-Driven Tumors: These patients have specific genetic drivers. "We actually have targeted therapies that can go and treat these patients," he noted.
2. Wild-Type Tumors: For patients without these specific mutations, "immune checkpoint blockade has really changed the outcome,” Ahluwalia said.

The current research frontier isn't just about choosing one therapy; it’s about the synergy between drugs and technology. While radiosurgery has traditionally been the backbone of treatment, Ahluwalia is excited about "combining targeted therapy, antibody-drug conjugates [ADCs] or immune checkpoint blockade with radiosurgery to give the best outcomes to our patients with a good quality of life."

Navigating Toxicity and Sequencing

Despite the excitement, treating the brain presents unique biological hurdles. One of the most significant challenges is the presence of systemic disease. A patient may have a stabilizing brain lesion but active disease in the liver or bone, creating a complex sequencing puzzle for doctors.

Historically, whole-brain radiation forced oncologists to halt systemic treatments, potentially allowing the cancer to spread elsewhere. Ahluwalia pointed out that modern radiosurgery allows systemic treatment to continue in most cases. However, new therapies bring new questions.

"Some of our research has now been focused on ADCs, because there [are] some initial data that there may be a higher incidence of radiation necrosis when you combine radiosurgery and ADCs," Ahluwalia said.

To solve this, his team is working on clinical trials to determine the best way to schedule these treatments—potentially decreasing radiation doses where possible—to ensure they are "getting great outcomes but decreasing the toxicity that these patients face."

A Message to the Community: From Months to Years

Perhaps the most striking takeaway from Ahluwalia is the change in survival expectations. He urged his colleagues in the community to view brain metastases through a lens of optimism.

"We are living in the greatest era of innovation," he said. "I would say we should provide hope to our patients... because a decade or 2 decades back, patients with brain metastases only lived 6 to 12 months. Now, a number of our patients with brain metastases are living 3, 4, or 5 years out."

He stressed that the key to this success is the "multidisciplinary management" involving medical oncologists, radiation oncologists, and neurosurgeons. For complex cases, he encourages community oncologists to partner with centers of excellence.

"Collaboration, hope, and excitement is my message to my colleagues in the community," he concluded.

REFERENCES

1. Metastatic brain tumors. Johns Hopkins Medicine. Accessed February 13, 2026. https://tinyurl.com/3zw7ra9s

2. Conger K. Lung cancer cells covertly thrive in brain under guise of protection, Stanford Medicine study finds. Stanford Medicine. October 23, 2023. Accessed February 13, 2026. https://tinyurl.com/msrt2sb8