Professor Albert Chan Chi-yan (left) and Dr Chiang Chi-leung collaborate once more to develop the innovative 'cocktail' strategy—Locoregional therapy and immunotherapy (LRT-IO) approach. This method features three treatment stages: stereotactic beam radiotherapy (SBRT) with optional transarterial chemoembolisation (TACE), followed by immunotherapy (IO).
An interdisciplinary research team from the Department of Surgery and Department of Clinical Oncology, School of Clinical Medicine at the LKS Faculty of Medicine of the University of Hong Kong (HKUMed), has demonstrated a durable and lasting response to a novel treatment – combined locoregional therapy and immunotherapy (LRT-IO) – for advanced liver cancer patients. The study marks the first investigation into the long-term outcomes for patients with locally advanced liver cancer receiving this treatment. The researchers identified key factors associated with a complete response, and found that this pioneering approach is safe, effective and sustainable. The findings were recently published in the journal JAMA Oncology [link to the publication]
Background
Advanced liver cancer is often considered incurable, but it can sometimes be converted to a treatable stage through a combination of therapies, potentially leading to curative surgery. Research'dynamic duo' Professor Albert Chan Chi-yan, Clinical Professor and Li Shu Fan Medical Foundation Professor in Surgery in the Department of Surgery, and Dr Chiang Chi-leung, Clinical Assistant Professor in the Department of Clinical Oncology, both under the School of Clinical Medicine, HKUMed, explored a new approach combining locoregional therapy and immunotherapy to achieve this conversion in patients with inoperable liver cancer. This innovative 'cocktail' strategy consists of three treatments: stereotactic beam radiotherapy (SBRT) with optional transarterial chemoembolisation (TACE), followed by immunotherapy (IO).
In previous studies, the team found that the cancer completely disappeared in 42% of patients after treatment, as evidenced by MRI or CT scans – even without curative surgery. While the LRT-IO approach has shown significant effectiveness in treating advanced, inoperable liver cancer, its long-term effects remained unclear. This study aimed to investigate the long-term outcomes of this novel LRT-IO approach and identify the factors contributing to a complete long-lived response to this treatment.
Research methods and findings
The HKUMed research team closely monitored 63 patients with locally advanced unresectable liver cancer who had been treated with the LRT-IO approach between January 2018 and December 2022. The patients, with a median tumour size of 10cm, were followed up regularly for a median duration of almost three years. During this period, 29 patients (46%) achieved a complete response, and two-thirds of them remained cancer-free at the time of data cutoff in June 2023.
Remarkably, the patients with a complete response were over twice as likely to be alive after three years than those without (three-year overall survival rate of 76% vs. 28%). The overall survival rate for patients with a complete response was comparable to that of patients who underwent curative surgery. While approximately one-third of the patients experienced a recurrence of their cancer, 60% of these patients were eligible for curative surgery as a primary treatment option. These findings clearly indicated that achieving a complete response significantly improves long-term outcomes for patients with advanced liver cancer.
'Our study provides long-term data that confirms our previous findings: the LRT-IO approach is a potentially curative treatment for large, unresectable liver cancer, with a 46% complete response rate, and a 75% survival among patients who achieved a complete response,' explained Dr Chiang Chi-leung.
Significance of the study
Previously, an advanced liver cancer diagnosis left patients with few treatment options. The LRT-IO approach now offers new hope – not only for managing this late-stage disease, but potentially curing it. The new research demonstrates the long-term effectiveness of the LRT-IO approach for advanced liver cancer patients, revealing that nearly half experienced a complete response from LRT-IO treatment alone, without the need for curative surgery. Despite these encouraging results, concerns about cancer recurrence remain, especially given the high rate of recurrence in liver cancer. These follow-up findings contribute critical evidence supporting the LRT-IO approach as a safe and effective long-term treatment option.
For patients who are elderly, medically unfit, or have difficult disease sites where surgery is not feasible, this study shows for the first time in the literature that LRT-IO, followed by a 'watch-and-wait' approach is a feasible option. This is the largest study to date on patients with advanced liver cancer treated with LRT-IO and the first to examine the long-term health outcomes of this treatment. A key takeaway from this study for liver cancer clinicians is the merit of the 'watch and wait' strategy. This may be a viable clinical management route for patients with a complete response to LRT-IO, as shown by the relatively high survival rates.
In 2024, a similar treatment approach known as 'START-FIT', designed by the same research team was included in the National Guidelines for the Management of Liver Cancer in China (2024 Edition). The research team is optimistic that the LRT-IO approach will also be incorporated into future guidelines as a result of this cutting-edge research. 'Professor Chan and I have continued to promote the use of this novel treatment in various local and national conferences. There are an increasing number of tertiary centres in Hong Kong that have adopted this LRT-IO strategy in their clinical practice. We hope to generate a guideline in Hong Kong to incorporate such practice in the near future,' asserted Dr Chiang.
'It will always be our passion and mission to explore novel and effective ways to tackle this deadly but common cancer,' said Professor Albert Chan Chi-yan, who led the research with Dr Chiang Chi-leung.
About the research team
The research was led by Professor Albert Chan Chi-yan, Clinical Professor and Li Shu Fan Medical Foundation Professor in Surgery in the Department of Surgery; and Dr Chiang Chi-leung, Clinical Assistant Professor in the Department of Clinical Oncology, both under the School of Clinical Medicine, HKUMed.
