HCC is a huge healthcare burden in Hong Kong and is one of the top 5 cancers in terms of incidence and mortality in Hong Kong. Patients with advanced HCC are treated with immunotherapy-based as first-line treatment as a standard of care. At the moment, there is limited evidence to guide subsequent treatments after patients progressed on immunotherapy. Oligoprogression is a term used to describe patients who had limited progression (usually less than 3 sites) on systemic therapy, with the rest of the lesions controlled. Previous studies in non-HCCs have shown that addition of locoregional treatment (e.g. radiotherapy) may prolong the use of systemic therapy, resulting in improved survival, but this has been relatively unexplored for HCC. In this prospective, single-arm study, we aim to evaluate the treatment outcome, efficacy and safety of the addition of radiotherapy to oligoprogressive sites for patients who had limited progression on First-line Immunotherapy.

Inclusion Criteria:

1. Patients aged ≥ 18 years old

2. ECOG performance 0 to 1

3. Confirmed diagnosis of HCC

4. Oligoprogression on first-line immunotherapy, as defined as ≤ 5 lesions (intra- and extrahepatic lesions all together; vascular tumor thrombus is counted as one lesion)

   • First-line immunotherapy that are allowed in this study include atezolizumab plus bevacizumab, durvalumab plus tremelimumab, durvalumab, nivolumab and ipilimumab, which are approved by the FDA and have been used in Hong Kong.

5. Progressed lesion(s) amenable to SBRT:

   • For intrahepatic progression:

     • Number of intrahepatic progression ≤ 5
     • Total intrahepatic tumours ≤ 10
     • Maximum sum of HCC ≤ 20cm
     • Any one HCC ≤ 20cm
     • Normal liver volume minus intrahepatic GTV > 700cc
     • Mean liver dose ≤ 15Gy
     • No measurable common or main branch biliary duct involvement
     • No direct tumor invasion into the stomach, duodenum, small bowel or large bowel

   • For extrahepatic progression:

     • Maximal tumor size ≤ 7cm
     • Respective dose constraints of organ at risks as listed on the UK 2022 Consensus on Normal Tissue Dose-Volume Constraints for Oligometastatic, Primary Lung and Hepatocellular Carcinoma Stereotactic Ablative Radiotherapy can be met and ASTRO guideline.

6. Prior radiofrequency ablation (RFA) or trans-arterial chemoembolization (TACE) are eligible

7. Child-Pugh A liver function

8. Life expectancy longer than 12 weeks

9. At least one measurable treatment lesion according to RECIST 1.1

10. Written informed consent must be obtained prior to any study related procedures

11. Adequate haematological function (Hb ≥ 8.5g/dL; Plt ≥ 50x10^9/L; ANC ≥ 1.0x10^9/L; INR ≤ 1.5)

12. Adequate hepatic function (albumin ≥ 28g/L; Bilirubin ≤ 2.5xULN; ALT < 5 times upper limit normal)

13. Adequate renal function (serum creatinine ≤ 1.5 times the upper limit of normal range; Na ≥ 130mmol/L; K ≥ 3.0mmol/L)

14. Able to read, understand and provide written consent

Exclusion Criteria:

1. History of another malignancy except appropriately-treated BCC of skin or CIN of cervix during the last 5 years
2. Previous radiotherapy to the abdomen
3. Previous yttrium-90 chemoembolization
4. Repetitive history of non-healing wounds or ulcers within 2 months of inclusion
5. Pregnant or lactating females at any time during the study
6. Active autoimmune disease requiring systemic therapy in the past 2 years
7. Diagnosis of immunodeficiency (including HIV)
8. Ongoing corticosteroid therapy >10mg prednisone daily