Study determines higher dosage of radioembolization to treat liver cancer improves survival rates

A study led by clinician-scientists and researchers from the National Cancer Centre Singapore (NCCS) and Singapore General Hospital (SGH) has determined the benefits of using a higher dosage of radioembolization treatment using yttrium-90 (Y-90) microspheres, than previously recommended, for liver cancer. Patients who received this elevated dose had significantly better outcomes than those who did not. The study results, which are potentially practice changing, were published in the journal Liver Cancer in September 2024.

Primary liver cancer, or hepatocellular carcinoma (HCC), is the third leading cause of cancer-related death and the sixth most common cancer worldwide. The overall prognosis of HCC is poor, with less than 20% of patients surviving five years past diagnosis. One of the reasons for poor outcomes is late diagnosis and poorly efficacious therapy especially in late states of HCC.

Treatment for locally advanced hepatocellular carcinoma (HCC) varies greatly and, as a result, so do clinical outcomes. HCC can present with vascular invasion, which is when tumor cells have invaded blood vessels. HCC with vascular invasion is frequently treated with radioembolization using (Y-90) microspheres.

Y-90 is a minimally invasive treatment that first gained popularity as a treatment option for HCC in the 2000s. Y-90 delivers high doses of radiation via the bloodstream to tumor cells in the blood or tumors in the liver. However, the relationship between Y-90 dosage and clinical outcomes in HCC patients and its optimal dosage for HCC treatment has not been determined till now.

Determining optimal dosage for a promising liver cancer treatment

To address this gap in knowledge, a team of clinicians and scientists studied the outcomes of 413 locally advanced HCC patients treated with Y-90 therapy between January 2008 and May 2019 at SGH and NCCS. This is the largest single-institution unresectable HCC cohort treated with Y-90 (resin) therapy study to date.

Patients were divided into two groups based on the tumor absorbed dose of Y-90: those who received ≥ 150 Gy and those that did not. The unit Gray (Gy) denotes the amount of radiation a unit volume of tumor has received. The ≥ 150 Gy dosage was based on the mean dosage of the patient cohort, which was 154.7+/- 80.4. Earlier studies have suggested that delivery of 120 Gy to HCC should confer disease control.

The team found that patients who received ≥150 Gy of Y-90 therapy had significantly better overall survival outcomes, living almost 15 months longer than those who did not. In addition, 17% of the study cohort or 70 patients whose tumor burden was successfully regressed or downstaged by Y-90 subsequently underwent curative treatments, such as surgical resection, thermal ablation or liver transplantation.

This process of downstaging tumors so that the patient has the opportunity to receive curative treatment is also known as conversion therapy. The patients who underwent conversion therapy after Y-90 showed remarkably prolonged survival outcomes, living 4 times as long compared to those who did not receive curative treatments.

What findings mean for liver cancer patients

“Y-90 has been a valuable option for treating liver cancer that cannot be surgically removed but the radiation dose must be adequate without causing harm to patients. Now that we know a higher dose can potentially help achieve better outcomes, it can guide treatment planning and discussions between patients and their doctors,” said Dr. Chen Kaina, first author of the study and Associate Consultant in the Department of Gastroenterology & Hepatology, SGH.

“Liver cancer remains a lethal disease that is of higher prevalence in Asia. End-to-end research is key to understanding its molecular underpinnings, enhancing diagnosis and improving treatment so that patients have better outcomes. This study is one of the many we are conducting on liver cancer. We hope that our combined efforts studying the disease will move the needle and take liver cancer from lethal to treatable,” said Professor Pierce Chow, senior author of the study and Senior Consultant Surgeon, Division of Surgery and Surgical Oncology, SGH and NCCS.

As a next step, the team has launched a multi-national trial that combines Y90 with immunotherapy for HCC.