Pattern of progression and post-progression survival following transarterial embolisation: An analysis of the TACE-2 and TACTICS trials.

In patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib, post-progression survival (PPS) is marked by the pattern of progression. Our aim was to assess the influence of the pattern of progression to selective internal radiotherapy (SIRT) in PPS among patients with HCC. A retrospective analysis of patients treated with SIRT between 2003 and 2015 was conducted, excluding those with a single nodule < 5cm or with metastases. Four patterns of progression to SIRT were defined: target tumour growth, non-target tumour growth, new intrahepatic disease, and new extrahepatic disease. PPS was calculated from the time of progression based on RECIST 1.1 criteria. Out of the 102 patients who met the selection criteria, 76 progressed after a median follow-up of 15months. Median PPS was 6.5months (95% CI 3.8-9.3months). Patients who progressed at pre-existing lesions had a better PPS (median 12.5months) than those who progressed with new lesions inside or outside the liver (median 4.2months) (p = 0.02). In a Cox model adjusted by liver function and systemic inflammation, the pattern of progression had a hazard ratio of 1.64 (95% CI 0.92-2.93; p = 0.093). In a cohort of HCC patients treated with SIRT, the pattern of progression associated with worst survival was the development of new intrahepatic lesions or extrahepatic metastases.

For decades, stratification criteria for first-line clinical studies have been highly uniform. However, there is no principle or consensus for restratification after systemic treatment progression based on immune checkpoint inhibitors (ICIs). The aim of this study was to assess the patterns of disease progression in patients with advanced hepatocellular carcinoma (HCC) who are not eligible for surgical intervention, following the use of immune checkpoint inhibitors. This is a retrospective study that involved patients with inoperable China liver stage (CNLC) IIIa and/or IIIb. The patients were treated at eight centers across China between January 2017 and October 2022. All patients received at least two cycles of first-line treatment containing immune checkpoint inhibitors. The patterns of disease progression were assessed using RECIST criteria 1.1. Different progression modes have been identified based on the characteristics of imaging progress. The study's main outcome measures were post-progression survival (PPS) and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method to compare the difference among the four groups. Subgroup analysis was conducted to compare the efficacy of different immunotherapy combinations. Variations in the efficacy of immunotherapy have also been noted across patient groups exhibiting alpha-fetoprotein (AFP) levels equal to or exceeding 400ng/mL, in contrast to those with AFP levels below 400ng/mL. The study has identified four distinct patterns of progress, namely p-IIb, p-IIIa, p-IIIb, and p-IIIc. Diverse patterns of progress demonstrate notable variations in both PPS and OS. The group p-IIb had the longest PPS of 12.7m (95% 9.3-16.1) and OS 19.6m (95% 15.6-23.5), the remaining groups exhibited p-IIIb at PPS 10.5 months (95%CI: 7.9-13.1) and OS 19.2 months (95%CI 15.1-23.3). Similarly, p-IIIc at PPS 5.7 months (95%CI: 4.2-7.2) and OS 11.0 months (95%CI 9.0-12.9), while p-IIIa at PPS 3.4 months (95%CI: 2.7-4.1) and OS 8.2 months (95%CI 6.8-9.5) were also seen. Additional stratified analysis was conducted and showed there were no differences of immunotherapy alone or in combination in OS (HR= 0.92, 95%CI: 0.59-1.43, P=0.68) and PPS (HR= 0.88, 95%CI: 0.57-1.36, P=0.54); there was no significant difference in PPS (HR=0.79, 95% CI: 0.55-1.12, P=0.15) and OS (HR=0.86, 95% CI: 0.61-1.24, P=0.39) for patients with AFP levels at or over 400ng/mL. However, it was observed that patients with AFP levels above 400ng/mL experienced a shorter median progression of PPS (8.0 months vs. 5.0 months) after undergoing immunotherapy. In this investigation of advanced hepatocellular carcinoma among Chinese patients treated with immune checkpoint inhibitors, we identified four distinct progression patterns (p-IIb, p-IIIa, p-IIIb and p-IIIc) that showed significant differences in PPS and OS. These findings demonstrate the heterogeneity of disease progression and prognosis after immunotherapy failure. Further validation in large cohorts is necessary to develop prognostic models that integrate distinct progression patterns to guide subsequent treatment decisions. Additionally, post-immunotherapy progression in patients with AFP levels ≥400ng/mL indicates a shortened median PPS. These findings provide valuable insights for future personalized treatment decisions.

229 Background: HCC progression may be due to tumor growth or new intrahepatic or extrahepatic lesions. RECIST does not discriminate between progression patterns even though the prognosis may differ (Reig, Hepatology 2013). REG improves overall survival (OS) in patients with HCC who progress during SOR treatment (HR 0.63; 95% CI 0.50, 0.79; P &lt; 0.001). This exploratory analysis aimed to validate the pattern of progression concept in a global cohort treated with prior SOR and to assess the impact of REG on survival by prior progression. Methods: Adults with HCC who tolerated SOR and had radiologic progression during SOR, Child–Pugh A liver function, and ECOG PS 0–1 were randomized 2:1 to REG 160 mg/day or placebo during weeks 1–3 of each 4-week cycle. Progression during SOR was due to tumor growth or new lesions. Post-progression survival (PPS) was the time from progression on SOR until death. Results: Baseline characteristics of the 573 randomized patients (REG = 379; placebo = 194) were balanced; median age was 63 years, 88% were male, 87% were BCLC stage C, 29% had macrovascular invasion, and 72% had extrahepatic disease. Hazard ratios favored REG irrespective of pattern of progression during prior SOR, but differed according to progression pattern (Table). Conclusions: The development of new extrahepatic lesions is associated with worse survival irrespective of treatment. REG provided an OS benefit, regardless of progression pattern. Progression pattern may be a key prognostic parameter and should be considered in future trial design and analysis. Clinical trial information: NCT01774344. [Table: see text]

BackgroundHepatocellular carcinoma (HCC) early-stage treatment options include potentially curative surgeries. Locoregional treatments are recommended for nonsurgical intermediate stage patients, and those awaiting liver transplant. Systemic therapy is generally recommended for...

Sorafenib improves overall survival (OS) of patients with hepatocellular carcinoma (HCC) in the absence of objective response. Thus, time to tumor progression (TTP) is used to capture benefits of novel molecular agents, but proof of its surrogacy with survival is lacking. Furthermore, survival predictors upon progression are not established and there is a need to characterize postprogression survival (PPS) and assess with time-dependent covariates analysis if it is influenced by progression pattern, and not solely by simultaneous impairment of liver function and performance status. We prospectively followed HCC patients treated with sorafenib. Clinical and biochemical evaluation were done every 4 weeks. Radiologic assessment of progression was done at week 4 and then every 8 weeks using RECIST 1.1. The progression pattern was divided into: intrahepatic/extrahepatic increase in tumor size, new intrahepatic lesion, and new extrahepatic lesion (NEH). We included 147 patients (hepatitis C virus [HCV] 57.1%, performance status [PS] 0 83.6%, Child-Pugh A 82.3%, and BCLC-C 47.3%). The median OS was 12.7 months and its independent predictors (hazard ratio [HR], 95% confidence interval [CI]) were: baseline BCLC 2.49 [1.66-3.73], PS 1.86 [1.12-3.10], registration during follow-up of Child-Pugh B or Child-Pugh C scores (2.36 [1.51-3.69] and 2.89 [1.62-5.15], respectively), definitive sorafenib interruption 2.48 [1.54-4.01], and TTP 3.39 [1.89-6.1]. The presence of NEH 2.42 [1.32-4.44] is also an independent predictor of OS and PPS in patients with radiologic progression. Tumor progression is a surrogate of survival but its impact varies according to progression pattern. Thus, PPS is influenced by progression pattern and this is key in prognostic prediction and second-line trial design and analysis.

Background & AimsRadiological progression patterns to first‐line sorafenib have been associated with post‐progression and overall survival in advanced hepatocellular carcinoma, but these associations remain unknown for therapies in second‐ and later‐line settings. This post hoc analysis of REACH and REACH‐2 examined outcomes by radiological progression patterns in the second‐line setting of patients with advanced hepatocellular carcinoma treated with ramucirumab or placebo.MethodsPatients with advanced hepatocellular carcinoma, Child‐Pugh A and Eastern Cooperative Oncology Group Performance Status 0 or 1 with prior sorafenib were randomized to receive ramucirumab 8mg/kg or placebo every 2 weeks. Among 625 patients with ≥1 progression pattern (new extrahepatic lesion [including new macrovascular invasion], new intrahepatic lesion, extrahepatic growth or intrahepatic growth), data were analysed by trial and for pooled individual patient data for REACH‐2 and REACH (alpha‐fetoprotein ≥400 ng/mL). Cox models evaluated prognostic implications of progression patterns on overall and post‐progression survival.ResultsPost‐progression survival was worse among those with new extrahepatic lesions in REACH (HR 2.33, 95% CI 1.51‐3.60), REACH‐2 (HR 1.49, 95% CI 0.72‐3.08) and the pooled population (HR 1.75, 95% CI 1.12‐2.74) compared to other progression patterns. Overall survival was also significantly reduced in those with new extrahepatic lesions across studies. Ramucirumab provided an overall survival benefit across progression patterns, including patients with new extrahepatic lesions (HR 0.56, 95% CI 0.39‐0.80) in the pooled population.ConclusionsThe emergence of new extrahepatic lesions in the second‐line setting is a poor prognostic factor for post‐progression survival. The benefit of ramucirumab for overall survival was consistent across progression patterns.

510 Background: Radiological progression patterns have long been recognized as prognostic indicators in hepatocellular carcinoma (HCC) treated with tyrosine kinase inhibitors. However, their impact in the era of immune checkpoint inhibitors (ICIs) remains underexplored. This study investigates the prognostic significance of progression patterns in advanced HCC patients receiving ICI-based therapies. Methods: We conducted a retrospective cohort study of 293 patients with radiologically confirmed disease progression following ICI treatment at Queen Mary Hospital between January 2015 and September 2023. Progression patterns were categorized as intrahepatic growth, new intrahepatic lesions, extrahepatic growth, and new extrahepatic lesions. Multivariate Cox regression analyses were performed to assess their impact on overall survival (OS) and post-progression survival (PPS), adjusting for ALBI score and AFP levels. Results: Intrahepatic growth was significantly associated with poorer OS in both the first-line (HR 1.905, 95% CI 1.268–2.861; p = 0.002) and overall cohorts (HR 1.632, 95% CI 1.203–2.213; p = 0.002). Extrahepatic growth consistently predicted reduced OS (HR 1.728, 95% CI 1.305–2.290; p &lt; 0.001) and PPS (HR 1.771, 95% CI 1.330–2.360; p &lt; 0.001) across all treatment subgroups. New extrahepatic lesions were associated with inferior OS in the overall (HR 1.402, 95% CI 1.054–1.865; p = 0.020) and first-line populations (HR 1.556, 95% CI 1.060–2.285; p = 0.024), and with poorer PPS in patients receiving ICI combined with anti-VEGF agents (HR 1.842, 95% CI 1.089–3.116; p = 0.023). In contrast, new intrahepatic lesions did not demonstrate significant prognostic impact on PPS in adjusted analyses (HR 0.938, 95% CI 0.708–1.243; p = 0.658). Conclusions: In advanced hepatocellular carcinoma treated with immune checkpoint inhibitors, intrahepatic growth and extrahepatic expansion—particularly of pre-existing lesions—are independently associated with poorer overall and post-progression survival. These findings highlight the prognostic relevance of radiological progression patterns in the immunotherapy era and suggest that both intra- and extrahepatic disease dynamics warrant close surveillance. Integrating systemic therapies with timely locoregional interventions may offer a path to improved outcomes in this patient population.

Since the approval of sorafenib, no other agent has been proven to show survival benefits in clinical trials involving patients with advanced hepatocellular carcinoma (HCC) resistant to sorafenib. Prognostic factors for survival after tumor progression in sorafenib-treated patients are critical for designing second-line trials. To determine the factors affecting the post-progression survival (PPS) after sorafenib treatment, additional analyses were conducted using fixed data obtained from our previous prospective study. Data on patients with advanced HCC treated with sorafenib were analyzed in view of patient characteristics at the time of tumor progression and the progression pattern (intra-/extrahepatic growth or emergence of new intra-/extrahepatic lesions). Of the 89 enrolled patients, 70 were diagnosed with disease progression according to the Response Evaluation Criteria in Solid Tumors version 1.1. Multivariate Cox's regression analysis revealed that Child-Pugh scores of ≥7, macrovascular invasion (MVI), and alpha-fetoprotein of >400 ng/mL were independent predictors of poor PPS. Although both extrahepatic metastasis (EHM) and MVI were characteristics of advanced HCC, EHM was not determined as a prognostic factor. Additionally, the emergence of new extrahepatic lesions also served as an independent indicator of a poor prognosis. The PPS of the patients was well stratified according to the index based on the sum of these prognostic factors, ranging from 0 to 4. Child-Pugh score of ≥7, AFP of >400 ng/mL, MVI, and new extrahepatic lesions at the time of progression may be utilized to assess the prognosis and taken into consideration when designing second-line trials.

Regorafenib as Second-Line Systemic Therapy May Change the Treatment Strategy and Management Paradigm for Hepatocellular Carcinoma

539 Background: Although the combination of atezolizumab and bevacizumab (ATZ + BEV) is a standard treatment for advanced hepatocellular carcinoma (HCC), strategies for addressing treatment failure and prognostic factors of post-progression survival remain unestablished. Methods: We conducted a multicenter retrospective study to evaluate post-progression survival following ATZ + BEV treatment in patients with advanced HCC. We classified the patients into four groups: BCLC stage B with or without new intrahepatic lesions (BCLCp-B1 and BCLCp-B2, respectively) and BCLC stage C without or with new extrahepatic lesions (BCLCp-C1 and BCLCp-C2, respectively) at the time of progression. Results: Of the 204 patients who started ATZ + BEV treatment between October 2020 and September 2022, 110 showed disease progression, with 25, 8, 55, and 22 showing the BCLCp-B1, BCLCp-B2, BCLCp-C1, and BCLCp-C2 stages of the disease, respectively. Specifically, patients with the BCLCp-B1 stage of the disease showed better overall survival than those with the BCLCp-B2, BCLCp-C1, and BCLCp-C2 stages (hazard ratios: 2.19 (95% confidence interval [CI], 0.61–7.86), 2.16 (95% CI, 1.13–4.11), and 2.97 (95% CI, 1.42–6.23) for HCC stages BCLCp-B2, BCLCp-C1, and BCLCp-C2, respectively). Via multivariable analysis, we identified the BCLCp-C1 and BCLCp-C2 stages, as well as performance status, Child-Pugh class, and alpha-fetoprotein as poor prognostic factors for post-progression survival. Conclusions: BCLCp-B1 stage was identified as a better prognostic factor for post-progression survival following ATZ + BEV treatment compared with BCLCp-B2 stage as well as BCLCp-C1 and BCLCp-C2 stages. This may help in making decisions regarding subsequent treatment after ATZ + BEV.

Streamlining TARE or personalizing SIRT? Different philosophies to treat different HCCs with Yttrium-90…

The study aims to analyze the impact of different progression patterns and tumor burden size on survival of HCC patients, as well as their interactions, through a retrospective cohort study. The study involved 538 patients who had undergone treatment with sorafenib and had shown radiographic progression. The progression pattern was analyzed using Cox regression by including an interaction term between progression pattern and tumor burden, which was then visualized through a graphical analysis. Tumor burden was categorized into low, medium, and high subgroups based on the six-and-twelve criteria, allowing for an exploration of the effect of progression pattern on survival in different tumor burden situations. Compared to patients with only intrahepatic progression (NIH/IHG) with an overall survival (OS) of 14.1/19.9 months and post-progression survival (PPS) of 8.1/13.1 months respectively, patients with extrahepatic lesions (NEH/EHG) had worse overall and postprogressive survival (OS: 9.3/9.2 months, PPS: 4.9/5.1 months). The hazard ratio for extrahepatic progression (NEH/EHG) compared to intrahepatic progression (NIH/IHG) at low, medium, and high tumor burden were [HR 2.729, 95%CI 1.189-6.263], [HR 1.755, 95%CI 1.269-2.427], and [HR 1.117, 95%CI 0.832-1.499], respectively. The study concluded that the interaction between the tumor progression patterns and tumor burden significantly affects the prognosis of HCC patients. As the tumor burden increases, the sensitivity of the patient's risk of death to the progression pattern decreases. These findings are valuable in personalized treatment and trial design.

427P - Prognostic Factors for Post-Progression Survival in Patients Receiving Radical Treatment for Glioblastoma Multiforme

Heterogeneity of Radiological Progression Patterns and Association with Outcomes in Patients with Metastatic Prostate Cancer

BackgroundThe SITC Immunotherapy Resistance Taskforce recently defined primary and secondary resistance to anti-PD-1 therapy,1 yet there is little data that compares these two scenarios. In particular, detailed radiological dynamics of...