Y90 Radioembolization

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, but it can be difficult to treat. It’s often not caught until its later stages, and it occurs most frequently in people with chronic liver conditions, such as cirrhosis caused by hepatitis B or hepatitis C. For some of these patients, surgery is not an option, and they have to consider other treatment types.

Two UT MD Anderson investigators have spent much of their careers researching how to help patients with hepatocellular carcinoma live longer — and they recently unlocked a new treatment for patients across the globe.

Armeen Mahvash, M.D., a professor of Interventional Radiology who treats patients with radioembolization and conducts clinical research, and S. Cheenu Kappadath, Ph.D., a professor of Imaging Physics who is an expert in patient imaging and radiation dosimetry, knew that a procedure called Y90-radioembolization could kill the cancer and yield durable responses.

But the results hadn’t been replicated in nationwide or multi-center clinical trials, and that was preventing the treatment from becoming widely accessible to patients beyond UT MD Anderson.

That is, until recently.

In July 2025, they shared the interim results of DOORwaY90, a clinical trial for which they were co-national principal investigators (PIs). It demonstrated that this treatment was exceptionally successful in treating unresectable hepatocellular carcinoma. All patients in the DOORwaY90 clinical trial had 100% tumor control, and no progression of the tumor could be seen on any scans through one year of follow-up. These results were so strong that the Food and Drug Administration (FDA) gave approval for the use of SIR-Spheres as a first-line treatment against unresectable and unablatable hepatocellular carcinoma tumors.

“This is really opening the door for our patients. It’s truly practice-changing work,” says Mahvash.

Developing a new treatment for hepatocellular carcinoma

Years of prior clinical data demonstrated that Y-90 wasn’t consistently effective for HCC patients. But then DOORwaY90 emerged, showing overwhelmingly positive results.

What changed?

Mahvash and Kappadath knew the difference in clinical outcomes between their work and those at other hospitals: the precise delivery of the appropriate amount of radiation to the correct disease location(s) in the liver. In other words, patient-specific dosimetry and targeted delivery.

Previous studies and other clinical practices had not consistently accounted for these considerations, but at UT MD Anderson, it had been a critical part of radioembolization treatment planning for over a decade.

In the summer of 2023, they published the results of the RAPY90D trial – a single-center prospective study demonstrating some success in using Y-90-glass radioembolization in patients with HCC. This brought them one step closer to bringing this treatment to more patients. Now they could use this study as the model upon which they could build the next clinical trial. But this trial would be larger and include more treatment centers.

From the start, DOORwaY90 was different from many other trials. It was known as an investigator-initiated trial, or IIT, meaning it was developed wholly by the PIs — not a pharmaceutical or medical device company — and then taken to other centers. This is not the usual path for most multi-center clinical trials.

Before the trial began, Mahvash and Kappadath also recognized that consistent treatment planning and patient management were essential to the success of a prospective interventional trial. In order to maximize the chance for success, they taught investigators at each of the participating hospitals across the country how to perform patient imaging and its proper use for treatment planning dosimetry for curative response. They started with 65 patients. Eventually, the study grew to include 100 patients across 18 U.S. centers. The difference was remarkable.

Benefits of Y90 for HCC patients

During the Y90 procedure, targeted delivery of SIR-Spheres — tiny, radioactive beads made of resin — is administered through the hepatic artery to the liver cancer cells at the appropriate radiation dose. Using SIR-Spheres — as opposed to other types of radioactive beads that had been used in the past — offered other benefits as well. They deliver up to 40 times more radiation than conventional cancer radiation therapy, which uses a machine to aim high-energy radiation beams from outside the body into the liver. 

Conventional radiation is also given five days a week for several weeks. SIR-Spheres are typically delivered in one session. The beads continue to release radiation over the course of two weeks, gradually decreasing to insignificant levels, with few side effects.  

Doctors know that they’ve hit their target almost immediately after administering the beads. Patients can go home a few hours after the treatment is delivered, and they leave knowing that their tumor has been hit and they’ll have some sort of positive result. In fact, Mahvash gives each of his patients a video that shows the treatment hitting the tumor.

Patients can generally resume their regular activities within two days. The most common side effect is fatigue — the same as with traditional radiation.  

“This shows that doing better treatment planning will give you outstanding results,” Mahvash says.

‘Only possible here’ can now be possible anywhere

Mahvash first began working with SIR-Spheres nearly 20 years ago. Before that, he had worked as a mechanical engineer, but after just a few years, he experienced what he jokingly calls a “mid-life crisis at 23” and enrolled in medical school. He pursued a residency in radiology and became a fellow at UT MD Anderson.

It was then that he first found SIR-Spheres. He had been looking for his niche and thought technology was interesting. But eventually, he began to hit a wall in his work.

“Not being a physicist, there were parts that were out of my realm,” he says.

Mahvash’s mentor introduced him to Kappadath, a leading physicist with a reputation for incredible accuracy and a deep understanding of imaging. He also happened to have an interest in SIR-Spheres.

Like Mahvash, Kappadath had started his professional career in another field: astrophysics. After getting his Ph.D. in astrophysics and completing a fellowship where he worked on space missions, he decided to explore medical imaging and completed a research fellowship at MD Anderson. Medical physics, with its cutting-edge science and technology and potential for tremendous societal impact, hooked him on the field. He pursued didactic training through MD Anderson UTHealth Houston Graduate School and completed a clinical residency in medical physics to eventually become a faculty member at UT MD Anderson.

Mahvash and Kappadath began working closely together around 2010. Over the course of 15 years, they became the leading global experts in their field in 90Y-radioembolization. They’ve worked on eight clinical trials and published over 50 peer-reviewed articles — all in the field of Y90 radioembolization.

“I really could not have done this without Cheenu,” says Mahvash.             

“It goes both ways,” adds Kappadath.

A new chapter for radioembolization

The FDA approval of SIR-Spheres marks a new chapter for radioembolization as a therapy and for patients with unresectable hepatocellular carcinoma.

Both Mahvash and Kappadath agree that UT MD Anderson was the only place this progress could have been made. It took the right focus on collaboration and team science, coupled with resources, large patient volumes and unique expertise.

“This work was only possible here,” Kappadath says.

Now, these patients might have the chance to undergo a liver transplant. And in addition to transforming the lives of these patients, Kappadath and Mahvash have also changed the way researchers will conduct future studies with this work. They’ve demonstrated that careful delivery of adequate radiation dose to targeted locations after appropriate training and coordination was possible in a large multi-center prospective clinical trial. They have published articles on their methodology and trial design. Newer clinical trials on radioembolization using advanced dosimetry treatment planning can be conducted in a similar way.

Now, Mahvash and Kappadath are continuing to educate teams at cancer centers internationally.

“Stopping with 100 patients is not enough,” Mahvash says. “Stopping with a positive study is not enough."

“We need to be able to treat patients beyond UT MD Anderson and even the United States,” Kappadath adds.

Now, they plan to take the work that was once only possible here and enable it around the world through education and clinical collaboration.

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