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Yttrium-90 Microspheres May Increase Survival for Patients With Liver Cancer
Deborah Brauser

March 19, 2010 (Tampa, Florida) — An interventional radiology treatment using intra-arterial yttrium-90 (Y-90) microspheres (TheraSphere, MDS Nordion) shows promise in prolonging life for patients with hepatocellular carcinoma, according to results from a longitudinal cohort study presented here at the Society of Interventional Radiology (SIR) 35th Annual Scientific Meeting.

"More than 75% of hepatocellular carcinoma patients can't have surgery to remove their liver tumors, but this minimally invasive treatment may benefit them and give them more time," Riad Salem, MD, professor of radiology, medicine, and surgery, and director of interventional oncology at the Robert H. Lurie Comprehensive Cancer Center at Northwestern Memorial Hospital in Chicago, Illinois, told meeting attendees during his presentation.

"While patients aren't cured, their lives are being extended and their quality of life is improving," he added.

A Treatment for Patients Without Many Options

About 18,500 cases of primary liver cancer are diagnosed each year. The most common form is hepatocellular carcinoma — a tumor that begins in the main cells of the liver. Liver cancer treatment options are limited, Dr. Salem reminded SIR meeting attendees.

"Historically, chemotherapy drugs and external radiation therapy have been ineffective at curing inoperable liver cancer," said Dr. Salem in a statement. "Additionally, because of the compromised liver function, physicians must be careful that cancer treatments do not cause additional liver damage and toxicity, which could lead to death."

This new outpatient treatment combines the radioactive isotope Y-90 into microspheres that deliver radiation directly into a tumor. Each microsphere "bead" is about the width of 5 red blood cells. These beads are injected through a catheter from the groin into the artery supplying blood to the tumor.

"This is a particularly elegant way to give patients cancer treatment that doesn't harm the healthy cells. Patients don't feel sick or have many of the side effects that happen with standard cancer treatments," said Dr. Salem. "It's like a seed implantation but with extremely high doses, and is very localized."

He noted that this is a procedure that they have been working on "methodically" for the past 10 years.

For this study, the investigators enrolled 291 patients (77% male, 25% were more than 75 years old, and 73% had multifocal disease) between December 2003 and December 2008, and administered 526 Y-90 treatments. The patients were subdivided by their Barcelona Clinic Liver Cancer (BCLC) staging system (A or B) and Child-Pugh liver function score (A or B). A total of 43% of the patients had portal vein thrombosis.

This "was a high-risk patient population, with most having multiple tumors," noted Dr. Salem. "The median tumor size was about 7 cm, but overall they ranged from 1 to 22 cm in size."

The researchers reviewed 1250 scans to assess time to progression and treatment response rate. They also evaluated toxicity and survival by cancer stage, and used Response Evaluation Criteria in Solid Tumors (RECIST) to measure tumor shrinkage.

"This is the largest worldwide series ever presented of the treatment of primary unresectable liver cancer using radiation microspheres," reported Dr. Salem. "Our goal was to identify which patients were really benefiting and which ones potentially are not the best candidates for this therapy."

Improved Results, Dramatic Tumor Shrinkage

Results showed that overall time to progression was 7.9 months (95% confidence interval [CI], 6.0 - 10.3). "By oncologic standards for this disease, this is a very promising finding," said Dr. Salem.

Using World Health Organization guidelines, the overall response rate was 42%. Using the European Association for the Study of the Liver guidelines, the overall response rate was 57%.

Survival times differed significantly by cancer staging system (26.9 months for BCLC A vs 17.2 months for BCLC B) and by liver function score (17.2 months for Child-Pugh A vs 7.7 months for Child-Pugh B).

Child-Pugh B patients with portal vein thrombosis had the worst outcomes, with a median survival of only 5.6 months (95% CI, 4.5 - 6.7).

"Patients with Child-Pugh A disease, with or without portal vein thrombosis, benefited the most from Y-90 treatment, compared with those with type B disease (P = .002)," reported Dr. Salem.

The most common treatment-related adverse effects were fatigue (57%), vague abdominal pain (23%), and nausea/vomiting (20%).

NB!!!! Finally, the tumors from 58% of the patients followed long term were downstaged from T3 to T2, and 32 of the patients were considered transplantable.

"This was a really dramatic finding. We were able to shrink patients' [tumors] to potential transplant or cure," said Dr. Salem. "The concept of converting incurable disease to transplantable and potentially curable is certainly very appealing. In some cases, we were able to downstage from unresectable to resection/surgical removal, also a potential cure."

"These are early promising results and show that there is a defining and evolving role for Y-90 microspheres in primary liver cancer. Our study showed who can benefit from this treatment, letting us know how to triage patients and prognosticate based on the things that they and their families want to know," he summarized.

Dr. Salem noted that the part that he finds most interesting is "this concept of downstaging to potential cure. If you have a patient with an incurable condition that you can potentially downstage to a cure with surgery, surgical resection, or transplant, that is just very exciting."

He reported that his investigational team has started a new trial that randomizes patients to receive either the Y-90 treatment or "the more standard therapies, such as radiofrequency, ablation, or chemoembolization." Eventually, they hope to look at trials that combine the best of the therapies.

Practice Changing

"This almost sounds too good to be true," SIR president Brian F. Stainken, MD, adjunct professor of radiology at Boston University School of Medicine in Massachusetts and department chair at Roger Williams Hospital in Providence, Rhode Island, said to Dr. Salem during a press conference.

"We're looking at a disease that kills over 18,000 people a year, at people who don't have a clear curative surgical option," said Dr. Stainken, who was not involved in the study. "You're treating them with an outpatient procedure, with no hospitalization, that is very well tolerated and converting many of them to curable. Those that you don't [downstage], you're expanding their life span. Where does this fit in the context of cancer care?"

"The thing we've learned is how potent this radiation really is when administered in this manner," explained Dr. Salem. "It is very dramatic to see 20 cm tumors shrink to 5 cm and get resected. These are downstaging concepts we've talked about for years. And the very notion of taking someone who has a median survival of 3 to 6 months or 6 to 12 months and having 7 to 8 years of follow-up on them is almost unheard of in therapies."

"This really challenges the paradigm of what we thought we knew. Maybe in certain cases we really can convert people to cures," he added.

After Dr. Salem's presentation, Dr. Stainken told Medscape Radiology that the Y-90 treatment shows "a lot of promise" for these patients. "It's moved from the initial trials to a much larger series, and the data seem to be remarkably consistent in a disease without many good options."

He added that "this is a disease that is not rare and this is a solution that has minimal risk, minimal morbidity, and little to no recovery time. It's almost like a magical treatment, but it's proving itself through rigorous investigation."

It's also proving that it does have a role in treating this disease and is changing practice. It should be on the list of options for every patient with liver cancer to consider."

In the future, we need to determine "where it fits and how it can be integrated into other treatments that are currently available," concluded Dr. Stainken.

This study was supported by TheraSphere. Dr. Salem reports receiving funding "relevant to the Y-90 microspheres." Dr. Stainken has disclosed no relevant financial relationships.

Society of Interventional Radiology (SIR) 35th Annual Scientific Meeting: Abstract 34. Presented March 14, 2010.