Editor’s Note:
Hepatocellular carcinoma (HCC) is one of the most common malignancies in China, with most patients diagnosed in the intermediate to advanced stages. The formation of portal vein tumor thrombus (PVTT) is a critical indicator of HCC progression, and patients with HCC combined with PVTT have a very poor prognosis. Previous studies have shown that low-dose radiotherapy can extend the survival of HCC patients with PVTT. From July 6th to 8th, 2023, the 13th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2023) was held in Seoul, South Korea. At the conference, a team led by Academician Jiahong Dong, Dr. Gong Li, and Dr. Keran Li from Beijing Tsinghua Chang Gung Hospital, Tsinghua University, China, presented a clinical study (Abstract Number: PE-97), investigating whether PVTT is more sensitive to radiotherapy than the primary tumor and exploring the efficacy of downstaging treatment in HCC patients with PVTT through the combination of radiotherapy, anti-angiogenic medication, and immunotherapy. Hepatology Digest had the privilege of inviting Dr. Gong Li to share the results of this research and its clinical application prospects.
Research Methods:
From January 2019 to August 2022, patients with HCC diagnosed with PVTT based on imaging were selected and received combined treatment with radiotherapy, anti-angiogenic medication, and immune checkpoint inhibitors, followed by either liver resection or liver transplantation. Efficacy was assessed using the RECIST guidelines and pathological evaluation. Sensitivity to treatment was compared between the primary tumor and PVTT by analyzing residual tumors of the primary tumor and PVTT and the rate of pathological complete response (PCR).
Research Results:
In imaging studies, PVTT showed a more significant reduction than the primary tumor (P < 0.05). Based on pathological diagnosis, the residual tumor of the primary tumor was significantly higher than that of PVTT (P = 0.008). In pathological research, the PCR rate of the primary tumor was significantly lower than that of PVTT (21.42% vs. 78.57%, P = 0.008). Imaging analysis showed that 42.86% of patients had stable disease in the primary tumor, 57.14% had partial remission, while 50% of patients had stable disease in PVTT, and 50% had partial remission.
Research Conclusion:
The results of this study suggest that PVTT is more sensitive to radiotherapy than the primary tumor. The combination of radiotherapy, anti-angiogenic medication, and immunotherapy is expected to be an effective downstaging treatment option for patients with HCC combined with PVTT.
Expert’s Review
Dr. Gong Li: HCC combined with portal vein tumor thrombus is a manifestation of advanced HCC, and the treatment of these patients is quite complex. Previous studies have shown that radiotherapy is highly effective against tumor thrombus. Targeted therapy and immunotherapy are currently the first-line standard treatments for advanced HCC. Therefore, our team explored the beneficial combination of targeted immunotherapy with radiotherapy for patients with HCC combined with portal vein tumor thrombus.
Firstly, we found that the control effect of radiotherapy combined with targeted immunotherapy on tumor thrombus was much better than that on the primary lesion. By combining radiotherapy with targeted immunotherapy, we can effectively eliminate the tumor thrombus and achieve downstaging treatment of HCC. This lays the foundation for the transformational treatment of many inoperable advanced HCC patients.
Secondly, for patients with poor liver function, severe disease, combined with main portal vein tumor thrombus, and not suitable for surgery, we also explored the combination of radiotherapy, targeted therapy, and immunotherapy. After treatment, we were able to increase the 2-year survival rate of these patients, which significantly improved their survival. This was not achievable with previous treatment methods. This also provides treatment options for patients with advanced HCC.
Furthermore, Y90 is a hot topic in radiotherapy research in recent years. The team at Tsinghua Chang Gung Hospital, led by Academician Jiahong Dong, has completed a series of research projects, attracting widespread attention in the field. Our research confirms that radiotherapy is effective not only in early-stage HCC but also in patients with advanced portal vein tumor thrombus. We believe that in the future, with the continuous development of medical technology, radiotherapy techniques such as Y90 treatment and stereotactic body radiotherapy (SBRT) will play an important role in the combined treatment of HCC.
For advanced HCC patients with PVTT, according to the Chinese “Primary Liver Cancer Diagnosis and Treatment Guidelines,” we mainly adopt a combination of local treatment, immunotherapy, and targeted drug therapy. However, we have now included radiotherapy. Previous studies have shown that after combined treatment with radiotherapy, immunotherapy, and targeted therapy, many inoperable HCC patients can be transformed into operable patients, and their survival time is extended.
Based on the results of this research, we have found that PVTT is highly sensitive to radiotherapy. Therefore, we can consider incorporating radiotherapy into the treatment of patients with advanced HCC combined with PVTT, and radiotherapy can become an important treatment method for advanced HCC in the future. In the future, we will conduct further research through clinical trials, and we hope that the treatment regimen of radiotherapy combined with anti-angiogenic medication and immunotherapy can become a treatment strategy for this group of patients.
Reference:
Keren Li. Combined Radiotherapy, Anti-angiogenesis and Immune Checkpoint Blockade Inhibition of Portal Vein Tumor Thrombus in Hepatocellular Carcinoma. APPLE 2023 Abstract PE-97
