• Multi-disciplinary team found that radiation therapy known as Yttrium-90 radioembolisation (Y90-RE) increases anti-cancer immunity and improves tumour response in liver cancer patients. 
  • Study highlights potential to combine Y90-RE with immunotherapy drugs to enhance treatment efficacy.
  • An 11-country, multi-centre Asia-Pacific phase-III clinical trial led by National Cancer Centre Singapore showed that Y90-RE showed better tumour response and fewer side-effects compared to oral drug Sorafenib.
Singapore, 23rd April 2018

Ground-breaking translational research by a multi-disciplinary team from the National Cancer Centre Singapore (NCCS), Translational Immunology Institute (TII), SingHealth Duke-NUS Academic Medical Centre and the Singapore General Hospital (SGH) discovered that Yttrium-90 radioembolisation (Y90-RE), which is a form of radiation therapy, enhances the activation of immune cells with anti-tumour activity in patients with hepatocellular carcinoma (HCC), or primary liver cancer. This is in addition to the expected effects of radiotherapy, which is to kill cancer cells directly. Y90-RE boosts patients’ immune systems to fight the cancer and gives rise to sustained tumour response in HCC. 

Y90-RE is a minimally-invasive radiation treatment that delivers high-energy beta radiation directly to cancer tumours. It is currently being used as treatment for patients with tumours that are too advanced for surgery or liver transplant. Findings of the impact of Y90-RE on the immune system were published in scientific journal Gut in February 2018.

The team looked at 34 patients with intermediate and advanced HCC over two years. They studied specific T-cells populations (immune cells with anti-tumour activity) in the patients’ blood and within the liver cancer after Y90-RE treatment, and found that they significantly increased and remained elevated specifically in patients with sustained response. Of these 34 patients, 16 patients showed no further tumour progression and seven patients’ cancer tumours shrank sufficiently (downstaged) for subsequent liver resection. These seven patients were compared to another seven patients who had surgery for HCC without being downstaged with Y90-RE.

In another recent publication, the team reported the conclusion of a six-year long, 11-country Asia-Pacific phase-III clinical trial led by NCCS comparing Y90-RE with anti-cancer drug sorafenib in 364 patients. This clinical trial showed that while average survival rates were similar with the two treatment methods, patients treated with Y90-RE had significantly fewer side-effects and better tumour response. This 27-centre study was conducted under the auspices of the Asia-Pacific Hepatocellular Carcinoma Trials Group in collaboration with the Singapore Clinical Research Institute. Findings were published in the Journal of Clinical Oncology in March 2018. 

The findings complement each other. While the clinical trial showed that Y90-RE was an efficacious treatment for HCC patients, the translational research study explained how the radiation delivered by a single dose of Y90-RE radiation, which decreases significantly after three days, could induce a sustained therapeutic response ranging from three to six months after treatment in patients. The Y90-RE immunology study shed light on this when it showed that Y90-RE had an immunological impact on patients with HCC in addition to its radiation effect.

Prof Pierce Chow, Protocol Chair of the phase III trial and also corresponding author of translational research study said, “The combined findings of these two landmark studies confirmed the efficacy of Y90-RE and allowed us to understand the therapeutic mechanisms underpinning Y90-RE. It also suggests the potential combination of immunotherapy with Y90-RE, so as to enhance the efficacy of immunotherapy treatment for patients with liver cancer.” Prof Chow is Senior Consultant, Division of Surgical Oncology at NCCS and Course Director at Duke-NUS Medical School.

In addition to the clinical study, the team will next be looking at developing a prediction tool to determine which patients will benefit most from Y90-RE. 

Dr Valerie Chew, first and corresponding author of the Gut paper, Junior Principal Investigator at TII, said, “By studying immune cells in the circulatory blood system, we could potentially predict which patients would likely respond positively to Y90-RE, even before the treatment is applied. Additional information from in-depth profiling of immune cells can also help us to identify which immunotherapy drugs may strengthen the efficacy of the radiotherapy.” Dr Chew is also an Assistant Professor at Duke-NUS Medical School.

These studies were made possible with funding from the National Medical Research Council Singapore. Sirtex Medical also contributed with a research grant in the phase III clinical trial.

About National Cancer Centre Singapore
National Cancer Centre Singapore (NCCS) provides a holistic and multidisciplinary approach to cancer treatment and patient care. We treat almost 70 per cent of the public sector oncology cases, and they are benefiting from the sub-specialisation of our clinical oncologists. NCCS is also accredited by the US-based Joint Commission International for its quality patient care and safety. 

To deliver among the best in cancer treatment and care, our clinicians work closely with our scientists who conduct robust cutting-edge clinical and translational research programmes which have been internationally recognised. NCCS strives to be a global leading cancer centre and shares its expertise and knowledge by offering training to local and overseas medical professionals. For more info, please visit www.nccs.com.sg 

About Translational Immunology Institute
The SingHealth Duke-NUS Academic Medical Centre’s Translational Immunology Institute (TII) is a translational clinical research platform that aims to develop translational immunology in Singapore. TII uses the Immunomics platform, a powerful and dynamic model to study the regulation of the immune system by integrating information from several high through-put technologies including multiple phenotypical assays.

TII collaborates with researchers and clinician-scientists on clinically important medical conditions through translational studies on immunology and inflammation. Translational research bridges un-met needs between knowledge of basic sciences and its translation into medical practice and meaningful health outcomes. 

About Singapore Clinical Research Institute
Singapore Clinical Research Institute (SCRI) is a National Academic Research Organisation dedicated to enhance the standards of human clinical research. Its mission is to spearhead and develop core capabilities, infrastructure and scientific leadership for clinical research in Singapore. SCRI is a national clinical trials coordination centre that works with National Medical Research Council (NMRC) to assist the Ministry of Health in implementing clinical trials policy and strategic initiatives to support and develop clinical research competencies locally. In driving towards its vision, SCRI collaborates with clinicians to enhance Singapore’s clinical research and strengthen its expertise in executing multi-site, multi-national studies and the development of regional clinical research networks. SCRI is a wholly-owned subsidiary of MOH Holdings. http://www.scri.edu.sg 

About Y90-RE
Yttrium-90 radioembolisation (Y90-RE), also known as selective internal radiation therapy (SIRT) is an approved treatment for inoperable liver tumours. It is a minimally-invasive treatment that delivers high-energy beta radiation directly to the tumours. Y90-RE is administered to patients by interventional radiologists and nuclear medicine physicians, who infuse millions of radioactive microspheres (whose diameters are around 32.5 microns, or about one-third the diameter of a human hair) via a catheter into the liver arteries that supply blood to the tumours. The microspheres use the tumours’ own blood supply to deliver a dose of short-range radiation that is up to 40 times higher than conventional radiotherapy, while sparing healthy tissue. 

About SIRveNIB
In the SIRveNIB study conducted from 2010 - 2016 to compare the efficacy and safety of Yttrium-90 radioembolisation (Y90-RE) versus sorafenib in locally advanced HCC, the results had shown that patients treated with Y90-RE had fewer and less severe side effects. Tumour response was superior with Y90-RE and the median overall survival at 6 months for treatment by Y90-RE was also superior as compared to the oral Sorafenib drug. This study was conducted by the Asia-Pacific Hepatocellular Carcinoma Trials Group (AHCC) in collaboration with the NCCS and the Singapore Clinical Research Institute (SCRI) and supported by the National Medical Council Singapore and Sirtex Medical Limited. The results were analysed in 2017 and was first presented at ASCO in Chicago in June 2017. The results were published online in the Journal of Clinical Oncology on 2 March 2018. 

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