Liver cancer is challenging to treat as only around 20% of patients are diagnosed in the early stage, when patient outcomes are likely to be better. (Credit: iStock.com/Mohammed Haneefa Nizamudeen)
The primary liver cancer, hepatocellular carcinoma (HCC) is a challenging cancer to treat as only around 20% of patients are diagnosed in the early stage, when immediate surgery or local ablation can still be curative. In Singapore, it is the third most common cause of cancer deaths in males and fifth most common cause in females.
Data from the National Cancer Centre Singapore (NCCS) shows that the majority of HCC patients (46%) are diagnosed with locally advanced cancer including those with vascular invasion. A radiotherapeutic therapy called selective internal radiation with yttrium 90 (SIRT Y90) is an effective treatment for many patients in this category.
In Southeast Asia, SingHealth has treated more than 800 cases of HCC using SIRT Y90 since 2008. The volume of patients treated and expertise with this therapy makes SingHealth a centre of excellence for SIRT Y90, with training courses for doctors from the region held annually. A detailed analysis SingHealth's SIRT Y90 experience in treating HCC has recently been published by NCCS and Singapore General Hospital (SGH) in a leading medical journal, shedding light on how a higher radiation dose with SIRT Y90 has led to better patient outcomes.
Research key to better liver cancer outcomes
"Liver cancer is particularly common in Asia and can be deadly. End-to-end research is key to understanding the disease better, improving how we diagnose it and improving the effectiveness of treatments so that patients have hope of a cure," explained Professor Pierce Chow, Senior Consultant Surgeon at SGH and NCCS.
Prof Chow, along with his research team, recently conducted and published a study aimed at refining how SIRT-Y90 might be best utilised for locally advanced HCC. This is one of a number of studies that the team are conducting for liver cancer patients at various stages of disease.
A higher radioembolisation dose is more effective
SIRT Y90 or radioembolisation using Y-90 microspheres is a minimally invasive procedure that delivers radiation directly to tumours in the liver via the bloodstream. It became a widely used treatment option for HCC in the 2000s but the relationship between its dosage and clinical outcomes in patients has been unclear until now.
To address this gap in knowledge, Prof Chow and his team studied the outcomes and follow-up data of 413 HCC patients with locally advanced HCC treated with Y-90 at SGH and NCCS between 2008 and 2019. This was the largest study of its kind from a single institution focused on locally advanced HCC with longitudinal follow-up.
The unit Gray (Gy) indicates the amount of radiation a tumour has received. While past studies have suggested that a 120 Gy dose is the minimal dose required for SIRT Y90 to control the growth of HCC, the optimal dose to regress the tumour was unknown. In this new study, researchers studied clinical outcomes in patients those who received a 150 Gy dose or more of radiation, and those who received less than 150 Gy and found that patients who received a 150 Gy dose or more lived nearly 15 months longer than those who received a smaller dose.
For patients who had responded well to Y90 and had their tumours regress so that they could be surgically resected, there had been no previous consensus on the next best step for them. This new study showed that 17% of the patients who responded well to Y-90 treatment received further curative intent treatments, such as liver resection or transplantation. This group lived up to four times longer than those who did not undergo these treatments. These results support the emerging concept of conversion therapy, that patients who cannot initially undergo surgical resection for cure should receive treatment to downstage their cancer to facilitate subsequent curative therapy.
What these results mean for liver cancer patients
The findings, which were published in the journal Liver Cancer last year, is the largest cohort study which has shown how outcomes in liver cancer can be improved with conversion therapy using Y-90 followed by surgery. Findings from this study and from other publications have led to changes in clinical practice. Prof Chow hopes that ongoing research will further improve clinical outcomes in liver cancer and turn it from a previously rapidly progressive disease into one that is more treatable.
"This study is just one of many efforts we're making to tackle liver cancer," said Prof Chow, senior author of the study who is also the principal investigator of NCCS' Programme in Translational and Clinical Liver Research.
(From left) Liver Cancer study first author Dr Chen Kaina, Associate Consultant, Dept of Gastroenterology & Hepatology, SGH and senior author Prof Pierce Chow, Senior Consultant Surgeon, SGH and NCCS.
Patient Case Study – Cancer-Free After High-Dose Y-90 and surgery
In 2012, Doreen Ang was undergoing a routine health check when her doctor discovered her liver enzyme levels, also known as gamma-glutamyl transferase (GGT) levels, were very high. As a Hepatitis B carrier with a family history of liver cancer, she was at increased risk of developing the disease. Further scans indicated that Doreen had cirrhosis (liver scarring) and multiple tumours in the liver, one of which was 14.5cm in size. She was diagnosed with multi-focal locally advanced stage HCC and her tumour was technically not amendable to surgical resection at that point in time.
Doreen sought the care of Prof Chow who was then studying the use of Y-90 microspheres for liver cancer. At the time, Y-90 wasn't widely used, but Prof Chow recommended it for Doreen to control the growth of the tumour and to potentially shrink her tumours so that surgery might be possible in the future.
In 2012, Doreen underwent her first round of SIRT Y-90 treatment and received a 129.63 Gy dose. The treatment worked well, shrinking the largest tumour from 14.5cm to 10.7cm. Over the next year, she underwent more treatments, including radiofrequency ablation, which burns and removes smaller tumours, and a second round of Y-90 with a 197.34 Gy dose. By early 2014, the largest tumour had shrunk even more, and Prof Chow was able to carry out surgery for Doreen to remove the remaining cancerous tissue and resect three remaining tumours.
Today, 12 years later, Doreen is cancer-free. She continues to take medication to keep her liver healthy and sees her surgical oncologist for check-ups twice a year.
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