Prospective Study of Stereotactic Body Radiation Therapy as Bridging Therapy for Hepatocellular Carcinoma Patients on Waiting List for Liver Transplantation

Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. It is the third leading cause of cancer death in Hong Kong. Liver transplantation (LT) is the curative treatment of choice for HCC as it has the advantage of removing the tumour and also the premalignant cirrhotic liver. Milan (solitary tumour <5cm, or up to 3 tumours, each <3cm) and University of California San Francisco (UCSF) criteria (solitary tumour ≤6.5cm, up to 3 tumours with none >4.5cm, and total tumour diameter ≤8cm) provide the benchmark requirements for LT, at which a 5-year survival of >70% and recurrence rate ranging from 5-15% can be achieved. However, organ shortage and waiting time for liver grafts remain the greatest obstacles for deceased donor liver transplantation (DDLT). It has been reported that the waiting list dropout rate is 7 to 11% at 6 months and 38% at 12 months. Several therapeutic procedures including transarterial chemoembolisation (TACE) and stereotactic body radiation therapy (SBRT) have been studied as bridging therapy before DDLT, aiming at reducing waiting list dropout rate and recurrence after LT, and improving post-transplant survival. TACE is the most widely used bridging therapy with tumour necrosis rate of 25-57% on explant pathology.

However it is largely only feasible in patients with Child-Pugh Class A status. SBRT, through the delivery of extremely conformal tumouricidal radiation in a few fractions (usually ≤5) under real-time liver and tumour motion monitoring, is more fashionable. Prospective studies have shown a higher local control rate of 87-100% at 1 year, an overall survival of 60-69% at 2 years after SBRT for unresectable HCC with minimal radiation-induced liver disease (RILD) compared to TACE. Studies have also been made on the use of SBRT as bridging therapy. Computed tomography (CT) and magnetic resonance imaging (MRI) have traditionally been used to diagnose and monitor treatment response for HCC. Their sensitivity and specificity are comparable for lesions >2cm. MR imaging provides higher soft tissue contrast and addition of liver-specific contrast agent (gadoxetate disodium, Primovist) further improves detection of 1-2cm tumours, demonstrating 92.1% accuracy based on the Milan and UCSF guidelines. However MRI is subject to significant motion artefacts during scanning. 18F-fluorodeoxyglucose (FDG) PET-CT has been extensively studied in HCC staging and treatment response monitoring. Unfortunately, FDG PET-CT is only capable of detecting the more poorly-differentiated component of HCC. It was first found in Hong Kong in 2003 that 11carbon-acetate (ACC) can detect the more well-differentiated component and both FDG and ACC as dual tracers have an incremental value of diagnosing extra-hepatic metastases in comparison to FDG alone. It was further proven by our hepatobiliary surgical team that ACC improved overall sensitivity of diagnosis in the pre-transplant cohort.

Few studies have looked at PET-CT for treatment response evaluation. A previous study has shown that cohorts with higher standardised uptake value (SUV) ratios have higher responses to external radiotherapy than lower SUV ratios cohort. However, the population was small and the treatment regimens were inhomogeneous. Use of FDG PET-CT has been promising in assessing treatment response after TACE and Y-90 microspheres selective internal radiation therapy (SIRT). However, there are very few publications on dual tracer PET-CT scan to evaluate tumour response after SBRT.

In view of the above, the investigators have carried out a prospective study on HCC patients treated with bridging SBRT before LT. The investigators used dual tracer (FDG and ACC) positron-emission tomography with integrated computed tomography (PET-CT) and MRI with gadoxetate disodium as baseline and subsequent imaging assessment before and after SBRT, hoping the dual tracer PET-CT and MRI with gadoxetate disodium can help better identify those who benefit from SBRT and to prioritise those with poor response so that they can be better channeled to LT.