Two landmark studies led by SingHealth researchers show interesting new findings on a liver cancer therapy that has been in use for more than a decade.
The therapy – Y90-SIRT – refers to Selective Internal Radiation Therapy (SIRT) with yttrium-90 (or radio embolization), which is a way of controlling the growth of liver cancers too advanced to be removed by surgery at the time they were diagnosed.
The two studies were led by researchers from the National Cancer Centre Singapore (NCCS). The first study was a 27-centre, randomised controlled study in 11 Asia-Pacific countries. Randomised controlled trials provide the highest form of clinical evidence in medicine, known as level 1 evidence, because it compares two treatments under highly controlled conditions.
The study confirmed that the therapy is efficacious and safe for patients with locally advanced liver cancer, while the second study uncovered additional mechanisms that explain why it works so well.
The six-year randomised controlled study, which involved 360 patients, showed significant tumour regression and higher safety with Y90-SIRT compared to available oral cancer therapy.
“Tumour regression is important, as this potentially allows patients with locally advanced liver cancer to eventually be treated with liver resection or transplantation, which are curative modalities in early-stage liver cancers. Most liver cancer patients in Singapore are diagnosed with locally advanced cancers,” said Professor Pierce Chow, Senior Consultant, Division of Surgical Oncology, NCCS, who initiated both studies.
The findings were published in leading cancer journal, Journal of Clinical Oncology earlier this year.
While this clinical trial confirmed that the therapy leads to good response in patients and is safe, it is the second study that explains the molecular mechanisms behind the good outcomes.
“These findings represent new advancement in the knowledge and treatment of liver cancer. They have provided us with strong scientific data that confirms and explains why this therapy works,” said Prof Chow. SingHealth currently has the most experience with this therapy in the Asia-Pacific after having treated almost 500 cases.
Therapy has fewer side effects
Y90-SIRT, which delivers radioactive micro beads directly into tumours through the blood vessels leading to tumours, causes fewer side effects than Sorafenib, an oral drug for liver cancer.
Prof Chow cited the case of a patient in his ’70s with an 8 cm tumour in his liver. Two weeks after the Y90-SIRT therapy, apart from a loss of appetite, he could carry on with his daily activities.
Six months later, his tumour had shrunk by half and he was downstaged to early-stage liver cancer. His cancer was subsequently resected and he remained well.
“The side effects of the standard oral cancer therapy drug include skin peeling, tiredness, diarrhoea, and so forth. But the side effects of Y90-SIRT were fewer and milder. It is a less toxic drug, and over a six-month period, the patient survival rate was much higher,” said Prof Chow.
While Y90-SIRT has been used for more than a decade, level 1 evidence was only available in 2017 through the NCCS-led SIRveNIB Asia-Pacific study and the European SARAH study, which was conducted at the same time with a study design based on the Asia-Pacific one. Both studies have since been published.
The second study results
The second study found that in addition to killing cancer cells through radiation, Y90-SIRT also boosts the body’s immune system, which leads to long-lasting effects.
Results, published in leading scientific journal Gut this year, showed that Y90-SIRT enhanced the body’s immune system to fight cancer.
Dr Valerie Chew, Junior Principal Investigator, SingHealth Translational Immunology Institute, and lead author of the study, said the Y90-SIRT therapy activates immune cells to attack cancer.
“We discovered that immune cells in the body that can fight cancer are enriched in patients who had the therapy,” she said.
The discovery is important when seen in the context of immunotherapy, a treatment that harnesses the body’s immune systems to recognise and attack cancer cells. But how well patients respond to immunotherapy can be limited by the number of immune cells they have. If the number of immune cells is low, even with immunotherapy, cancer treatment might not be effective.
Dr Chew said this suggests that the Y90-SIRT treatment, which induces an increase in immune cells in patients’ bodies, may work very well in combination with immune-therapy.
“Y90-SIRT in combination with the existing immunotherapy may enhance the immune response in patients,” she said.
The article has been re-printed from the November/December 2018 issue of Singapore Health, the flagship publication of the SINGHEALTH DUKE-NUS ACADEMIC MEDICAL CENTRE.