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426 Background: Preclinically, radiation therapy for tumors was well known to reverse the immunosuppressive state by reprograming the tumor microenvironment. The combination of radiotherapy and immune checkpoint inhibitors (radio-immunotherapy) has renewed interest in clinical practice, and different irradiation dose may contribute diversely to immune response and abscopal effect. This pilot study aimed to assess the antitumour activity of the anti-PD-1 inhibitor Camrelizumab combined with different irradiation dose in patients with advanced hepatocellular carcinoma (HCC). Methods: Between April 2020 and January 2021, 20 patients with advanced HCC were prospectively enrolled in this pilot study. Five patients were treatment-naive and 15 patients were diagnosis as progressive diseases after previous treatment. For each patient, one to 3 intrahepatic and/or extrahepatic lesions were selected to irradiate. Camrelizumab was concurrently administered with 200mg on the first day of radiation and then every 3 weeks until disease progression, or unacceptable toxicity. Eligible patients were randomly assigned to receive 3 irradiation doses: low-dose group of 30Gy/10 fractions(3Gy/fx), intermediate-dose group of 40Gy/10 fractions (4Gy/fx), and high-dose group of 50Gy/10 fractions (5Gy/fx). Results: Nine patients had intrahepatic lesions (8 of macrovascular invasion) and 11 had extrahepatic metastases. The median number of treatment lines receiving immunotherapy of Camrelizumab was 2 (range 1-5). Enrolment to the 30Gy group was halted after 2 patients due to the poor clinical response. Finally, 2, 11, and 7 patients received the irradiation dose of 30, 40, and 50Gy, respectively. Twenty-eight selected lesions were irradiated (partial lesions in 12 patients and all lesions in 8 patients). Grade 3 treatment-related adverse events were observed in 4 patients, including 2 thrombocytopenia and 1 anaemia in the 40Gy group, and 1 anaemia in the 50Gy group. The median follow-up time was 12 months (range 7.0–18.0 months). There was a significant difference in PFS, but no difference in OS between the three groups. The median, 6- and 12-months PFS for the 30, 40, and 50 Gy groups were 1.7 months, 0% and 0% vs. 4.0 months (95%CI 1.7-6.3 months), 27.3% and 18.2% vs. 7.8 months (95%CI 4.1-11.5 months), 57.1% and 38.1%, respectively (P = 0.027). The median, 12-months OS were 11.4 months and 50% vs. 11.8 months and 34.6% vs. not reached and 66.7%, respectively (P = 0.229). The disease control rates were statistically different between the 30, 40, and 50Gy groups (50% vs. 54.5% vs. 100%, P = 0.039), whereas objective response rates were not significant different (0% vs. 45.5% vs. 71.4%, P = 0.123). Conclusions: Higher irradiation dose with 50 Gy in 10 fractions plus Camrelizumab may augment the radio-immunotherapy activity in advanced HCC with favorable PFS. The present study offers guidance for the dose selection of subsequent clinical trials. Clinical trial information: ChiCTR2000032375.

e16155 Background: External beam radiation therapy has been used as a palliative to radical treatment of hepatocellular carcinoma (HCC) depending on different tumor status, liver function and patient's general state of health. The existing models of HCC staging cannot perfectly predict the prognosis of radiotherapy. In this study, we aimed to set up a new staging system for radiotherapy-based treatment by incorporating bilirubin-albumin (ALBI) grade and tumor status for the prognostic classifications of HCC. Methods: This multicenter cohort study included 878 HCC patients who received radiotherapy-based treatment. A new staging system was established: stage I, solitary nodule without macrovascular invasion or 2-3 nodules with no more than 3.0 cm each other and PS 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with anyone more than 3.0 cm or ≥4 nodules and PS 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion or regional lymph node metastasis or distant metastasis and PS 0-2 (IIIa: ALBI-1 grade; IIIb:ALBI-2 grade); stage IV: ALBI-3 grade without stage I patient or/and PS score 3-4. The new modified staging system and the existing staging systems, such as the BCLC, TNM, CNLC staging systems were used for prognostic analysis. All patients were separated into different stages and substages. The long-term overall survival outcomes and time-dependent receiver operating characteristic (ROC) were analyzed. Results: A training cohort of 595 patients underwent stereotactic body radiotherapy (SBRT) from 2011 to 2017 and an external validation cohort of 283 patients underwent intensity-modulated radiotherapy (IMRT) from 2000 to 2013 were included into establishing and validating the new staging system. In the training cohort, the median follow-up time was 55 months (range, 6–100 months), and the new staging system had a good discriminatory ability to separate patients into different stages with 4 notably different curves and substages with 7 notably different curves. BCLC staging could not differentiate stage 0 to A, and stage C to D in these selected patients. TNM staging could not completely distinguish stage IIIb to IV, but also stage Ia to Ib. CNLC staging could not differentiate among stage IIIa, IIIb, and IV. In the external validation, the median follow-up time was 95 months (range, 9–120 months), and the new staging system also had a good discriminatory ability to separate patients into different stages with 4 notably different curves and substages with 7 notably different curves. The new staging system had a better area under curve of time-dependent ROC than BCLC, TNM and CNLC staging in both SBRT and IMRT cohorts. Conclusions: The new modified (Su’s) staging system could provide a good discriminatory ability to separate patients into different stages and substages after radiotherapy treatment. It may be used to supplement the other HCC staging systems.

e16115 Background: In the past clinical practice of radiotherapy for liver cancer, liver regeneration (LR) which is beneficial to the prevention or recovery of radiation-induced liver injury, has not received enough attention. In current study, we aimed to build and validate multivariate model for liver regeneration after radiation therapy for hepatocellular carcinoma (HCC) based on data from 2 prospective studies. Methods: Thirty patients treated with preoperative downstaging radiotherapy were prospectively included in the training cohort, and 21 patients treated with postoperative adjuvant radiotherapy were included in the validation cohort. Liver regeneration was defined as an increase of more than 10% of normal liver volume in the areas of the protected hepatic segment or lobe, without Child-Pugh class decreased and tumor progression compared to pre-radiotherapy. Model and nomogram of liver regeneration after radiotherapy were developed and validated. The cut-off points of each optimal predictors were obtained using receiver-operating characteristic analysis. Risk stratification based on the cut-off point was conducted to compare the proportion of patients with liver regeneration between subgroups. Results: After radiotherapy, 12 (40%) cases in the training cohort and 13 (61.9%) cases in the validation cohort experienced liver regeneration. The model and nomogram of liver regeneration based on SVs20 (standard residual liver volume spared from at least 20 Gy) and alanine aminotransferase (ALT) showed good prediction performance (AUC = 0.759) in training cohort and performed well (AUC = 0.808) in the validation cohort. The risk stratification according to the cutoffs of SVs20 with 303.4 mL and ALT with 43 U/L demonstrated clear differentiation in risk of liver regeneration between the training(P = 0.049) and entire cohort (P = 0.032). The proportion of patients with liver regeneration decrease progressively with 88.9% in high-probability group (ALT＜43 U/L and SVs20＜303.4 mL), 60% in high-intermediate probability group (ALT ≥43 U/L and SVs20＜303.4 mL), 43.75% in low-intermediate probability group (ALT＜43 U/L and SVs20≥303.4 mL) and 33% in low- probability group (ALT≥43 U/L and SVs20≥303.4 mL). Conclusions: SVs20 and ALT are optimal predictors for liver regeneration. This simple-to-use nomogram is beneficial to the constraints of normal liver outside the radiotherapy target area and make prognosis-based decision without complex calculations. Clinical trial information: ChiCTR1800015350. [Table: see text]