Prof Pisit shares recent health economic data from Thailand, revealing that the GAAD score is cost-effective for HCC surveillance among Thai population

Interview transcript:

Introduction

Hello everyone. I am Dr. Pisit Tangkijvanich from the Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Nice to meet all of you.

Could you provide an overview of the HECON study?

Hepatocellular Carcinoma, or HCC is one of the most common cancers in Thailand. From Global Cancer Statistic 2020, liver cancers, especially HCC, is the number 1 of cancer in Thailand with its highest incident in men and the fourth highest incidence in women. HCC is also a leading cause of cancer mortality in Thailand, like other countries in Southeast Asia. Together, these data highlight the importance of HCC as a major public health problem in our country.

The majority of HCC occurs in patients with chronic viral hepatitis, including hepatitis B and hepatitis C, fatty liver disease, and heavy alcohol consumption. It is generally accepted that the screening or regular surveillance for HCC should be performed in patients known to be at risk of this cancer, because the surveillance could identify HCC at an early stage and can improve the overall survival of the patients receiving curative treatment, such as surgical resection or liver transplantation.

Most professional society guidelines recommend using ultrasound and serum alpha fetoprotein, or AFP every 6 months for HCC detection in at-risk patients, such as those with cirrhosis. However, ultrasound (US) is operator dependent and its sensitivity is variable between centre to centre. Moreover, the US may have lower sensitivity in patients with obesity or fatty liver disease. As a result of US limitation, more accurate and accessible (surveillance) programs that could improve HCC early detection are required.

Currently, there are several emerging strategies for HCC detection. Among them, GAAD score which is derived from Gender, Age, and the combination of double tumour markers including AFP, and DCP (or PIVKA-II), is a promising tool for early detection of HCC. The available data show that GAAD score is superior to US for HCC diagnosis with a high sensitivity and specificity.

So the aim of our HECON study was to compare cost-effectiveness analysis between GAAD score with the standard-of-care using US plus AFP for HCC surveillance in Thai patients with compensated cirrhosis and chronic hepatitis B.

Could you walk us through the methodology employed in the HECON study and discuss key findings or results?

We selected cirrhotic patients in our study because these patients are at-risk of developing HCC as the incidence rate is more than 1.5% per year. For non-cirrhotic hepatitis B, we included this group of patients because the infection is highly prevalent in Thailand and also the subgroup of patients that at-risk of HCC, especially among males older than 40 years, and females older than 50 year, or those with family history of HCC.

So, we performed an economic model with Markov micro-simulation to simulate disease progression for individual patients, based on Thai population data. Literature review and interviews with Thai clinical experts were also used to identify model inputs that reflect current Thai clinical practice. Health states within the model were based on the patient’s underlying liver disease, such as cirrhosis or non-cirrhotic hepatitis B, HCC staging, such as early or late stage and treatment outcome according to the cancer stage.

Our results showed that GAAD score was cost-effective for Thai populations at the willingness to pay threshold of 160,000 THB (or approximately 4,400 USD). In fact, GAAD yielded lower cost and a better health outcome compared to US plus AFP. In addition, sensitivity analysis confirmed that routine surveillance using GAAD score had at least 55% probability of being cost-effective compared to no surveillance.

Together, our data indicate that GAAD score is suitable for use as a screening tool in Thailand.

In your opinion, what makes the HECON data important in the context of changing healthcare policies and decision-making in Thailand?

As the burden of liver cancer is high, HCC surveillance and control must be considered a public health priority. However, in Thailand, national efforts are focused on the control of viral hepatitis, which is primary prevention for HCC rather than the cancer surveillance.

So our data show that the new method using GAAD score is cost-effective, and importantly more feasible than US plus AFP testing, because GAAD score can be done the same day in the clinics. That will help in reducing several patient barriers such as transportation or logistical concerns.

Our data could play an important part in supporting the policymakers for making the best decision within limited resource in our country, to accelerate the reimbursement program for HCC surveillance in the future.

Are there any challenges or considerations that healthcare professional should be aware of when interpreting or applying the results of the HECON study in clinical practice?

Although our study provides promising results, there might be some concerns about the role of GAAD score as a screening tool for HCC detection. For example, in countries where there are inadequate facility for cancer therapy, the benefit of early detection might be reduced as limited number of patients could achieve curative treatment. In contrast, GAAD score is more suitable in community hospital or rural areas where access to US is limited, such as some areas in Thailand and many countries in the APAC region.

How do you foresee the results of the HECON study will help to inform clinicians’ HCC surveillance and clinical practice in the APAC region?

I think the results of HECON study can be used not only in Thailand but also can be applied to other country as well, which had a similar situation as Thailand, for example, the Philippines or Vietnam. Thank you.

The views and opinions expressed by Prof. Pisit Tankijvanich are his own views and opinions. Roche disclaims all liability in relation to these views and opinions.

Prof Tawesak Tanwandee and Asst Prof Sansnee Senawong demonstrates how digital algorithms are used in Siriraj Hospital for the early detection of HCC

Interview transcript:

TT: Prof. Tawesak Tanwandee

SS: Asst. Prof. Sansnee Senawong

Introduction

TT: My name is Tawesak Tanwandee, Professor of Medicine, Head of Division of Gastroenterology, Faculty of Medicine, Siriraj Hospital.

SS: Hello, I am the Assistant Professor of Medicine, Sansanee Senawong, Chief of the Immunology Department, Faculty of Medicine, Siriraj Hospital, Mahidol University.

TT: Siriraj Hospital is the largest and the oldest hospital in Thailand. As it is a large and highly advanced hospital, a large number of patients come to Siriraj Hospital annually.

SS: The laboratory of the Department of Immunology was certified by the international standard ISO 15189 since May 2006. It has passed the continuous evaluation and inspection for the ISO 15189:2012 standards to date.

TT: As we are a large hospital, we receive patients from other hospitals. The patients who are referred to our hospital are mostly terminally ill. They are already in the terminal stage of cancer.

What is the unmet need in HCC surveillance and diagnosis in Siriraj Hospital?

SS: In Thailand, liver cancer is one of the most common and leading causes of death in cancer patients in the country. We find that over 70% of patients who die of liver cancer are not admitted to the surveillance program, resulting in delayed diagnosis at the terminal stage and they pass away soon after.

TT: For patients at risk of liver cancer, we don’t always have the chance to screen them sufficiently at an early stage. Moreover, an early stage of liver cancer has no visible symptoms. Therefore, the patient does not realize they need to be tested.

SS: In terms of liver cancer, there are still challenges regarding the effectiveness of liver cancer surveillance.

TT: The standard practice for liver cancer surveillance today is composed of ultrasound scans and blood (biomarker) tests to check alpha fetoprotein (AFP) levels every 6 months.

SS: However, we find that the sensitivity rate is as low as 63%.

TT: Due to ultrasound capacity limitations, patients may have to wait for months or even a year for a scan. Ultrasound also relies heavily on the doctor conducting the scan and how meticulous they are. Patients who are obese or have been diagnosed with liver cirrhosis, may be difficult to detect liver cancer by ultrasound.

SS: As a laboratory, when choosing a test or a platform for our services, we must take into account the challenge of reporting laboratory results quickly and efficiently to keep up with the increasing laboratory workloads. Also, it has to minimize human errors as much as possible. We need to find an appropriate system that can support various biomarker testing and is reliable.

What is your clinical experience with PIVKA-II? How has it brought value to HCC diagnosis?

TT: The data from studies show that PIVKA-II was quicker to detect early stages of liver cancer in patients. Checking the levels of AFP and PIVKA-II at the same time is much more convenient to doctors. Therefore, a single blood test from the patient allows both tests to be run. When testing both, we see for some patients, that the level of AFP is normal but the PIVKA-II level is abnormal. This helps to alert the doctor to abnormalities in the patient.

SS: Providing PIVKA-II to use in our laboratory will help improve the efficiency of early liver cancer surveillance in the future.

What is your experience using digital algorithms? How does the digital algorithm bring value to enable early HCC diagnosis?

TT: There are about 50-60 patients who have used the digital algorithm. And it has been very beneficial to some patients.

SS: But due to the limitations of ultrasound access combined with the sensitivity performance of AFP, considering to add new biomarkers such as PIVKA-II and  the digital algorithm will play a very important role.

TT: When applying the digital algorithm, in practice, we have to add two other factors, age and gender. Sometimes, abnormalities in the AFP level or PIVKA-II level is detected. But the digital algorithm shows it as normal. The algorithm makes surveillance more accurate.

SS: According to many studies and the reports from the doctors who directly treat the patients, it was found that using PIVKA-II and the digital algorithm, compared to the results of AFP and ultrasound, which is considered standard/conventional practice, helps detect liver cancer at an early stage more efficiently.

What does your workflow using the digital algorithm look like?

TT: The digital algorithm has simplified the workflow. Every time a patient has a health check, it’s standard practice to run a blood test to check the liver health. With the blood sample, we can run the digital algorithm at the same time. This means the patient only needs to give one blood sample. Everything is done in one visit.

SS: After collecting the samples, the laboratory performs AFP, PIVKA-II, and digital algorithm tests. After the AFP and PIVKA-II test results are reported, the laboratory results will be combined with gender and age to automatically calculate the score. The result will be sent to the LIS or HIS system of the hospital, allowing the doctors to see the test results quickly. This makes the laboratory workflow more convenient and reporting of results faster.

TT: It’s very easy to interpret the result because there is only ‘positive’ or ‘negative’ (score). The doctors don’t need to interpret complicated numbers. When an abnormality in the digital algorithm is found, the doctor should conduct further (confirmatory) testing, especially using medical imaging techniques such as X-ray, CT or MRI scans.

What’s your expectation for the digital algorithm in the future?

TT: If we use the digital algorithm or PIVKA-II in addition to AFP, the liver cancer surveillance will likely be more accurate because this test already shares the same platform as their regular blood tests. And this will help us to decide if the patient is at risk of cancer, or need further surveillance tests. We might be able to detect the liver cancer at an earlier stage in more patients and provide successful treatment.

What is Siriraj  Hospital’s vision for the liver disease and HCC management?

TT: In patients who have been screened and found to have liver cancer, over 90% of them live longer than 5 years. In this case, it changes the patient’s life. If we can use other surveillance methods such as PIVKA-II or the digital algorithm, it might help to improve surveillance effectiveness.

SS: The department is very pleased to have been a part of an important step in using digital diagnostic tools which are helping liver cancer patients have a better quality of life and increase the survival rate.

TT: At Siriraj Hospital, we provide knowledge and raise awareness for everyone, which includes both patients and healthcare workers. So, the patients who are at risk of liver cancer, can receive surveillance regularly. We hope that in the future, every patient who is at risk of liver cancer, everyone in Siriraj Hospital, will receive the surveillance process regularly.

The views and opinions expressed by Prof. Tawesak Tanwandee and Asst. Prof. Sansnee Senawong are their own views and opinions. Roche disclaims all liability in relation to these views and opinions.