Hepatic Progression-free Survival Research Articles

Are survival outcomes dependent on the tumor dose threshold of 139 Gy in patients with chemorefractory metastatic colorectal cancer treated with yttrium-90 radioembolization using glass particles? A real-world single-Centre study.

To compare the survival and objective response rate (ORR) of the patients receiving estimated tumor absorbed dose (ETAD) <140 Gy versus ETAD ≥140 Gy in patients with advanced chemorefractory colorectal carcinoma liver metastases (CRCLM) treated with yttrium-90 transarterial radioembolization (90Y TARE). Between August 2016 and August 2023 adult patients with unresectable, chemorefractory CRCLM treated with 90Y TARE using glass particles, were retrospectively enrolled. Primary outcomes were overall survival (OS) and hepatic progression free survival (hPFS). Secondary outcome was ORR. A total of 40 patients with a mean age of 66.2 ± 7.8 years met the inclusion criteria. Mean ETAD for the group 1 (ETAD <140 Gy) and group 2 (ETAD ≥140) were 131.2 ± 17.4 Gy versus 195 ± 45.6 Gy, respectively. The mean OS and hPFS for group 1 versus group 2 were 12 ± 10.3 months and 8.1 ± 9.3 months versus 9.3 ± 3 months and 7.1 ± 8.4 months, respectively and there were no significant differences (p = 0.181 and p = 0.366, respectively). ORR did not show significant difference between groups (p = 0.432). In real-world practice, no significant difference was found in OS, hPFS and ORR between patients who received ETAD <140 Gy versus ETAD ≥140 Gy in patients with CRCLM, in this series. This study demonstrated that increased tumour absorbed doses in radioembolization may not provide additional significant advantage for OS and hPFS for patients with CRCLM.

Neuroendocrine Tumors of Unknown Primary in the Setting of Cytoreductive Hepatectomy.

Surgical cytoreduction for neuroendocrine tumor liver metastasis (NETLM) consistently shows positive long-term outcomes. Despite reservations in guidelines for surgery when the primary tumor is unidentified (UP-NET), this study compared the surgical and oncologic long-term outcomes between patients with these rare cases undergoing cytoreductive surgery and patients who had liver resection for known primaries. The study identified 32 unknown primary liver metastases (UP-NETLM) in 522 retrospectively evaluated patients who underwent resection of well-differentiated NETLM between January 2000 and December 2020. Tumor and patient characteristics were compared with those in 490 cases of liver metastasis from small intestinal (SI-NETLM) or pancreatic (pNETLM) primaries. Survival analysis was performed to highlight long-term outcome differences. Surgical outcomes were compared between liver resections alone and simultaneous primary resections to assess surgical risk distinctions. The UP-NET patients had fewer NETLMs (p = 0.004), which on the average were largerthan SI-NETLMs or pNETLMs (p = 0.002). Expression of Ki-67 was balanced among the groups. Major hepatectomy was performed more often in the UP-NETLM group (p = 0.017). The 10-year survival rate of 53% for UP-NETLM was comparable with that for SI-NETML (58%; p = 0.463) and pNETLMs (47%; p = 0.497). The median hepatic progression-free survival was 26 months for the UP-NETLM patients and 25 months for the SI-NETLM patients compared to 12 months for the pNETLM patients (p < 0.001). Perioperative mortality was lower than 2%, and severe postoperative morbidity occurred in 21%, similarly distributed among all the groups. The surgical risk and long-term outcomes for the UP-NETLM patients were comparable with those for other NETLM cases, affirming the validity of equally aggressive surgical cytoreduction as a therapeutic option in carefully selected cases.

Comparative outcomes of trans-arterial radioembolization in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease-induced HCC: a retrospective analysis.

Tumorigenesis in NAFLD/NASH-induced HCC is unique and may affect the effectiveness of trans-arterial radioembolization in this population. The purpose of this study was to retrospectively compare the effectiveness of trans-arterial radioembolization for the treatment of hepatocellular carcinoma (HCC) between patients with non-alcoholic steatohepatitis (NASH)/non-alcoholic fatty liver disease (NAFLD) and non-NASH/NAFLD liver disease. Consecutive patients with HCC who underwent TARE at a single academic institution were retrospectively reviewed. Outcome measures including overall survival (OS), local progression-free survival (PFS), and hepatic PFS as assessed by modified response evaluation criteria in solid tumors (mRECIST) were recorded. Kaplan-Meier and Cox proportional hazard models were utilized to compare progression-free survival and overall survival. 138 separate HCCs in patients treated with TARE between July 2013 and July 2022 were retrospectively identified. Etiologies of HCC included NASH/NAFLD (30/122, 22%), HCV (52/122, 43%), alcoholic liver disease (25/122, 21%), and combined ALD/HCV (14/122, 11%). NASH/NAFLD patients demonstrated a significantly higher incidence of type 2 diabetes mellitus (p < 0.0001). There was no significant difference in overall survival (p = 0.928), local progression-free survival (p = 0.339), or hepatic progression-free survival between the cohorts (p = 0.946) by log-rank analysis. When NASH/NAFLD patients were compared to all combined non-NASH/NAFLD patients, there was no significant difference in OS (HR 1.1, 95% C.I. 0.32-3.79, p = 0.886), local PFS (HR 1.2, 95% C.I. 0.58-2.44, p = 0.639), or hepatic PFS (HR 1.3, 95% C.I. 0.52-3.16, p = 0.595) by log-rank analysis. TARE appears to be an equally effective treatment for NASH/NAFLD-induced HCC when compared to other causes of HCC. Further studies in a larger cohort with additional subgroup analyses are warranted.

Chemoembolization Beyond Hepatocellular Carcinoma: What Tumors Can We Treat and When?

Liver metastases are the most common malignancy found in the liver and are 20 to 40 times more common than primary hepatic tumors, including hepatocellular carcinoma. Patients with liver metastases often present with advanced disease and are not eligible for curative-intent surgery or ablative techniques. The unique hepatic arterial blood supply of liver metastases allows interventional radiologists to target these tumors with transarterial therapies. Transarterial chemoembolization (TACE) has been studied in the treatment of liver metastases originating from a variety of primary malignancies and has demonstrated benefits in terms of hepatic progression-free survival, overall survival, and symptomatic relief, among other benefits. Depending on the primary tumor from which they originate, liver metastases may have different indications for TACE, may utilize different TACE regimens and techniques, and may result in different post-procedural outcomes. This review offers an overview of TACE techniques and specific considerations in the treatment of liver metastases, provides an in-depth review of TACE in the treatment of liver metastases originating from colorectal cancer, neuroendocrine tumor, and uveal melanoma, which represent some of the many tumors beyond hepatocellular carcinoma that can be treated by TACE, and summarizes data regarding when one should consider TACE in their treatment algorithms.

Real-world data of anlotinib for gastrointestinal tumors with liver metastases in China.

738 Background: Patients with advanced gastrointestinal tumors, such as gastric cancer (GC), colorectal cancer (CRC), esophageal squamous cell carcinoma (ESCC), biliary tract cancer (BTC) and pancreatic cancer (PC), often develop liver metastases with poor prognosis. Recent clinical studies have implicated that anlotinib (a novel anti-angiogenesis agent) could improve survival outcomes in gastrointestinal tumors with liver metastases, albeit with limited real-world evidence. This study aimed to report the efficacy and safety of anlotinib for gastrointestinal tumors with liver metastases in real-world practice. Methods: Demographic and clinical data of patients treated with anlotinib in any line of treatment for solid tumors with liver metastases (excluding primary liver cancer) was collected retrospectively through 5 large hospitals in China, between Jan, 2016 and Feb, 2023. The primary endpoints were progression-free survival (PFS) and objective overall response (ORR). Secondary endpoints included overall survival (OS), hepatic PFS (hPFS), hepatic ORR (hORR) and safety. In this abstract, we present data from patients with gastrointestinal tumors. PFS, hPFS and OS were estimated using the Kaplan-Meier method and compared using the log-rank test. Results: A total of 475 patients were enrolled in the study and 238 patients with gastrointestinal tumors were analyzed, including 73 (30.7%) GC, 71 (29.8%) CRC, 46 (19.3%) ESCC, 24 (10.1%) PC, and 24 (10.1%) BTC. 75.2% were &lt;75 years old, 82.4% were male, 63.9% had a normal body mass index (BMI) (18.5-24 kg/m2), 87.8% received third-line anlotinib, and 90.3% received anlotinib monotherapy. At data cut-off (Feb 28, 2023), the median PFS was 5.90 months (95% CI: 5.23-6.77), the median hPFS was 6.20 months (95% CI: 5.27-6.77), and the median OS was 9.37 months (95% CI: 8.40-NR). There was no statistically significant difference according to the tumor types in terms of PFS (p=0.66), hPFS (p=0.8) and OS (p=0.72). We also found patients with a BMI &lt; 18.5 kg/m2 had significantly shorter PFS (p=0.005) and hPFS (p=0.01). Adverse events (AEs) were manageable and tolerable, 30 (12.6%) patients had treatment-emergent adverse events (TEAEs) and 3 patients (1.3%) had ≥3 TEAEs. The most common treatment-related adverse events (TRAEs) were leukopenia (5.9%). Conclusions: To our knowledge, this is the first real-world report about anlotinib for gastrointestinal tumors with liver metastases in China, showed the clinical benefit of anlotinib in any line of treatment for gastrointestinal tumors with liver metastases and indicated that anlotinib could be a feasible treatment option in this specific population.

Phase II study evaluating the efficacy of PDS0301 in combination with hepatic artery infusion pump (HAIP) and systemic therapy for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma.

TPS586 Background: Treatment of advanced liver tumors continues to pose significant challenges. Despite advances in immunotherapies, including immune checkpoint blockade, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. The lack of robust clinical efficacy is likely myriad, including immunosuppression by the tumor microenvironment and poor susceptibility of these tumors to immune infiltration and surveillance. Interleukin-12 (IL-12) is a pro-inflammatory cytokine with extensive anti-tumor properties, but therapeutic development of recombinant human IL-12 (rhIL-12) was halted due to significant systemic toxicities. PDS0301 (formerly M9241) is a novel human monoclonal antibody (NHS76) fused to two IL-12 heterodimers. The NHS76 antibody specifically targets histone/DNA complexes in regions of cellular necrosis resulting in accumulation within tumors. Importantly, recent Phase I trials have shown PDS0301 monotherapy to be well tolerated. We hypothesize that synchronization of PDS0301 administration with tumor cell death induced by locoregional and systemic chemotherapies will demonstrate increased efficacy over standard of care therapy. Methods: This is a single center, non-randomized Phase II study to determine the safety and efficacy of PDS0301 in combination with floxuridine (FUDR) administered by hepatic artery infusion pump (HAIP) and systemic chemotherapies in patients with either unresectable metastatic colorectal cancer (mCRC) or intrahepatic cholangiocarcinoma (ICC). Eligibility criteria include histologically or cytologically confirmed colorectal adenocarcinoma metastatic to the liver (Cohort 1) or unresectable intrahepatic cholangiocarcinoma with no evidence of extrahepatic metastases (Cohort 2). Patients will receive HAIP-administered (FUDR) plus PDS0301 at a starting dose of 12mcg/kg in 28-day cycles. Beginning in cycle 2, systemic chemotherapy with FOLFOX (Leucovorin, 5-Fluorouracil [5-FU], and Oxaliplatin) or FOLFIRI (Leucovorin, 5-FU and Irinotecan) for mCRC or GemOx (Gemcitabine and Oxaliplatin) for ICC will be introduced. Patients will be evaluated for response at eight-week intervals. The primary endpoint is overall response rates to PDS0301 and HAIP/systemic combination therapy. Secondary objectives include hepatic progression-free survival (PFS), extra-hepatic PFS, overall survival, and safety. Scientific objectives include determination of microenvironment alterations through pre-and post-treatment biopsies as well as evaluation of peripheral immune subsets and cytokines. To date, we have enrolled 8 of 23 patients in Cohort 1. Clinical trial information: NCT05286814 .

Percutaneous ultrasound-guided radiofrequency ablation for patients with liver metastases from gastrointestinal stromal tumors

Objectives This study aimed to analyze the survival outcomes and prognostic factors of radiofrequency ablation (RFA) for liver metastases from gastrointestinal stromal tumors (GISTs). Methods Between March 2011 and November 2022, 34 patients (16 males; age range, 25–72 [median age, 52.5] years) who underwent RFA for liver metastasis from GISTs were included. The mean maximum diameter of metastatic lesions was 2.4 ± 1.0 (range, 1.1–5.2) cm. Survival curves were constructed using the Kaplan–Meier method and compared using the log-rank test. Multivariate analyses were performed using a Cox proportional hazards model. Results For 79 lesions among 34 patients, all targeted lesions were completely ablated. The mean hepatic progression-free survival (HPFS) period was 28.4 ± 3.8 (range, 1.0–45.7) months. The 1-, 3-, and 5-year HPFS rates were 67.2%, 60.5%, and 20.2%, respectively. Based on the univariate analysis, the number of metastatic tumors and tyrosine kinase inhibitors(TKI) therapy before RFA were prognostic factors for HPFS. Multivariate analysis showed that pre-RFA TKI therapy was associated with a better HPFS(p = 0.030). The mean overall survival (OS) period was 100.5 ± 14.1 (range, 3.8–159.5) months and the 1-, 3-, and 5-year survival rates were 96.9%, 77.1%, and 58.7%, respectively. Both univariate and multivariate analysis indicated that extrahepatic metastasis before RFA (p = 0.044) was a significant prognostic factor for OS. Conclusions Liver metastases from GIST exhibit relatively mild biological behavior. RFA is safe and effective, particularly in patients without pre-RFA extrahepatic metastases. Patients received targeted therapy before RFA can obtain an extended HPFS.

Circulating Regulatory T Cells: A Novel Marker Associated with Liver Metastasis and the Treatment Response of Transarterial Embolization in Gastroenteropancreatic Neuroendocrine Tumors

Introduction: The aim of this study was to investigate the role of circulating regulatory T cells (Tregs) as a novel marker associated with liver metastases and treatment response to transarterial embolization (TAE) in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Methods: Circulating Tregs, defined as the CD4+CD25+CD127low/− population, were examined by flow cytometry in peripheral blood mononuclear cells from patients with GEP-NETs. Clinicopathological parameters, radiologic response, and hepatic progression-free survival (hPFS) data were collected. Results: The association between circulating Tregs and clinicopathological parameters was analyzed in 139 GEP-NET patients. Higher Treg levels were significantly associated with more progressive clinical features, including a higher WHO grade, more advanced TNM stage, and the presence of liver metastases. A Treg level ≥8.015% distinguished between patients with and without liver metastases. Among a cohort of 51 GEP-NET patients who were subjected to TAE for reducing liver metastasis burden, patients with higher Treg levels depicted unfavorable responses and significantly reduced hPFS after TAE treatment. We also revealed that patients with Treghigh (≥8.975%) displayed significantly shorter median hPFS than patients with Treglow (Conclusion: Our data suggest that circulating Tregs are a novel immunological marker associated with liver metastases and treatment response to TAE in patients with GEP-NETs.

Neuroendocrine liver metastases treated using transarterial radioembolization: Identification of prognostic parameters at 68Ga-DOTATATE PET/CT

PurposeTo identify prognostic clinical and imaging parameters for patients with neuroendocrine liver metastases (NELMs) undergoing transarterial radioembolization (TARE). Materials and methodsForty-seven patients (27 men; mean age, 64 years) with NELMs who received TARE, along with pre-procedure liver MRI and 68Ga-DOTATATE positron emission tomography/computed tomography were included. Apparent diffusion coefficient and standardized uptake value (SUV) of three liver metastases, normal spleen and liver were measured. SUVmax or SUVmean were used for the calculation of tumor-to-organ ratios (tumor-to-spleen and tumor-to-liver ratios) using all possible combinations (including SUVmax/SUVmax, SUVmax/SUVmean, and SUVmean/SUVmean). Clinical parameters (hepatic tumor-burden, presence of extra-hepatic metastases, chromograninA, Ki-67 and bilirubin levels) were assessed. Overall survival, progression-free survival (PFS) and hepatic progression-free survival (HPFS) were calculated using Kaplan-Meier curves. ResultsMedian overall survival, PFS and HPFS were 49.6, 13.1 and 28.3 months, respectively. In multivariable Cox regression analysis, low Ki-67 (≤ 5%), low hepatic tumor-burden (< 10%), absence of extrahepatic metastases, and increased Tmean/Lmax ratio were significant prognostic factors of longer overall survival and HPFS. High baseline chromograninA (> 1330 ng/mL) was associated with shorter HPFS. Tmean/Lmax > 1.9 yielded a median overall survival of 69 vs. 33 months (P < 0.04), and a median HPFS of 30 vs. 19 months (P = 0.09). For PFS, high baseline SUVmax of NELMs was the single significant parameter in the multivariable model. SUVmax > 28 resulted in a median PFS of 16.9 vs. 6.5 months, respectively (P = 0.001). ConclusionHigh preinterventional Tmean/Lmax ratios, and high SUVmax on 68Ga-DOTATATE positron emission tomography/computed tomography seem to have prognostic value in patients with NELMs undergoing TARE, potentially aiding patient selection and management alongside conventional variables.

Efficacy and safety of irinotecan-eluting HepaSphere transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for unresectable colorectal liver metastases.

3585 Background: Both drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) are recommended for unresectable colorectal liver metastases (CRLM) treatment. However, the combined application of DEB-TACE and HAIC is not widely accepted. The aim of this single-center retrospective study was to evaluate the efficacy and safety of Irinotecan-eluting HepaSphere chemoembolization combined with HAIC for unresectable CRLM. Methods: Patients with age older than 18 years, histologically confirmed CRLM and treated with Irinotecan-eluting HepaSphere chemoembolization plus HAIC from Oct 2020 to Jan 2022 were enrolled. Patients who had synchronously received other local treatments were excluded. Hepatic progression-free survival (hPFS) and PFS were calculated using Kaplan-Meier method. Adverse events (AE) were evaluated with CTCAE 5.0. Results: The eligible population was 101, composed of 66 males and 35 females. Among them, 54% patients had one of KRAS or NRAS or BRAF gene mutation and ECOG of 62% patients was 1. In addition, 59% patients were refractory to second standard line or above systemic therapy and mean interventional treatment cycles were 3.3. As the follow-up cutoff date was Dec 31, 2022, median duration of follow-up was 17.9 months (95% CI,16.185-19.615). Median hPFS was 8.7 months (95% CI, 6.744-10.658) while median PFS was 6.2 months (95% CI, 5.048-7.352). For the patients who were refractory to second line or above systemic therapy, hPFS and PFS was 6.2 months (95% CI, 4.899-7.501) and 5.2 months (95% CI, 3.682-6.718) respectively. Overall survival has not been reached yet. There were 7 patients achieved clinical complete response. Overall response rate was 41.6% and disease control rate was 82.2%. There was no treatment-related death. 28 patients (27.7%) experienced grade 3 or higher toxicities. The most common treatment related AE were aspartate transaminase/alanine transaminase elevation (41.6%) and bilirubin elevation (40.6%). The hematologic AE included anemia (27.7%), leukopenia (27.7%), neutropenia (14.9%) and thrombocytopenia (28.7%). Conclusions: The combination of Irinotecan-eluting HepaSphere chemoembolization and HAIC is effective and safe for unresectable CRCLM, even for patients who are refractory to second or above systemic therapy, indicating it is a promising regional treatment with improved outcome.

Radioembolization with Yttrium-90 Glass Microspheres as a First-Line Treatment for Unresectable Intrahepatic Cholangiocarcinoma—A Prospective Feasibility Study

PurposeTo evaluate the safety and effectiveness of yttrium-90 (90Y) radioembolization as first-line treatment for unresectable intrahepatic cholangiocarcinoma (ICC). Materials and MethodsThis prospective study enrolled patients who had never received chemotherapy, liver embolization, and radiation therapy. The tumors were solitary in 16 patients, multiple in 8 patients, unilobar in 14 patients, and bilobar in 10 patients. Patients underwent transarterial radioembolization with 90Y-labeled glass microspheres. The primary end point was hepatic progression-free survival (HPFS). Secondary end points were overall survival (OS), tumor response, and toxicity. ResultsTwenty-four patients (age, 72.3 years ± 9.3; 12 women) were included in the study. The median delivered radiation dose was 135.5 Gy (interquartile range, 77.6 Gy). The median HPFS was 5.5 months (95% CI, 3.9–7.0 months). Analysis failed to identify any prognostic factor associated with HPFS. Imaging response at 3 months showed 56% disease control, and the best radiographic response was 71% disease control. The median OS from the radioembolization treatment was 19.4 months (95% CI, 5.0–33.7). Patients with solitary ICC had significantly longer median OS than patients with multifocal ICC: 25.9 months (95% CI, 20.8–31.0 months) versus 10.7 months (95% CI, 8.0–13.4 months) (P = .02). Patients with progression on the 3-month imaging follow-up had significantly shorter median OS than patients who had stable disease at 3 months: 10.7 months (95% CI, 0.7–20.7 months) versus 37.3 months (95% CI, 16.5–58.1 months) (P = .003). Two (8%) Grade 3 toxicities were reported. ConclusionsFirst-line treatment of ICC with radioembolization showed promising OS and minimal toxicity, especially in patients with solitary tumor. Radioembolization may be considered as a first-line treatment option for unresectable ICC.

Hepatic disease control in patients with intrahepatic cholangiocarcinoma correlates with overall survival.

The role of locoregional therapy compared to systemic chemotherapy (SYS) for unresectable intrahepatic cholangiocarcinoma (IHC) remains controversial. The importance of hepatic disease control, either as initial or salvage therapy, is also unclear. We compared overall survival (OS) in patients treated with resection, hepatic arterial infusion pump (HAIP) chemotherapy, or SYS as it relates to hepatic recurrence or progression. We also evaluated recurrence after resection to determine the efficacy of locoregional salvage therapy. In this single-institution retrospective analysis, patients with biopsy-proven IHC treated with either curative-intent resection, HAIP (with or without SYS), or SYS alone were analyzed. Propensity score matching (PSM) was used to compare patients with liver-limited, advanced disease treated with HAIP versus SYS. The impact of locoregional salvage therapies in patients with liver-limited recurrence was analyzed in the resection cohort. From 2000 to 2017, 714 patients with IHC were treated, 219 (30.7%) with resectable disease, 316 (44.3%) with locally advanced disease, and 179 (25.1%) with metastatic disease. Resected patients were less likely to recur or progress in the liver (hazard ratio [HR] 0.41, 95% CI 0.34-0.45) versus those that received HAIP or SYS (HR 0.58, 95% CI 0.50-0.65 vs. HR 0.63, 95% CI 0.57-0.69, respectively). In resected patients, 161 (64.4%) recurred, with 65 liver-only recurrences. Thirty of these patients received subsequent locoregional therapy. On multivariable analysis, locoregional therapy was associated with improved OS after isolated liver recurrence (HR 0.46, 95% CI 0.29-0.75; p = 0.002). In patients with locally advanced unresectable or multifocal liver disease (with or without distant organ metastases), PSM demonstrated improved hepatic progression-free survival in patients treated with HAIP versus SYS (HR 0.65; 95% CI 0.46-0.91; p = 0.01), which correlated with improved OS (HR 0.59, 95% CI 0.43-0.80; p < 0.001). In patients with liver-limited IHC, hepatic disease control is associated with improved OS, emphasizing the potential importance of liver-directed therapy.

Survival of Patients with Colorectal Liver Metastases after Transarterial Chemoembolization Using Irinotecan-Eluting Microspheres: A Single-Center Retrospective Analysis Comparing RECIST 1.1 and Choi Criteria

PurposeTo evaluate the factors that affected overall survival and hepatic progression–free survival using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and Choi criteria in patients with colorectal liver metastases treated with transarterial chemoembolization (TACE) using irinotecan-eluting microspheres (IEMs) who failed at least 1 line of systemic chemotherapy. Materials and MethodsA single-institution retrospective analysis was performed including patients with unresectable liver metastases from a colorectal primary malignancy and treated with IEM-TACE. Radiologic hepatic progression–free survival was measured using the RECIST 1.1 and Choi criteria. ResultsThe median patient age was 61.5 years, with 80 (67%) men. A total of 328 IEM-TACE procedures were performed during the study period. One hundred eighteen patients who failed at least 1 line of systemic chemotherapy before TACE demonstrated a median overall survival of 12.7 months. Overall survival was higher in patients who had previous primary resection (P < .05), prior ablation (P < .05), or completed the scheduled TACE treatments (P < .05) but was adversely affected by the presence of extrahepatic disease (P < .05) and larger preprocedural tumor burden (P < .01). Prior systemic chemotherapy lines (P = .98) and microsphere size (P = .34) did not affect survival. Partial radiologic response to treatment using the Choi criteria (n = 28, P < .01) correlated significantly with survival, a correlation not seen with the RECIST 1.1 measurements (n = 5, P = .13). ConclusionsA partial response to treatment of unresectable colorectal liver metastases treated by TACE with IEMs measured using the Choi criteria correlated significantly with improved survival, while RECIST 1.1 measurements did not.

The EPOCH trial: Identifying key patient subgroups to optimize treatment planning.

130 Background: The primary objective of the original EPOCH trial was to evaluate the potential benefit of adding transarterial radioembolization (TARE) with yttrium-90 glass microspheres to second-line chemotherapy (chemo) versus chemo alone in patients with liver-dominant metastatic colorectal cancer (mCRC). Randomization was stratified by key prognostic factors, including KRAS status; however, it did not account for ECOG status and baseline CEA levels. We present post-hoc analyses investigating the impact of prognostic factors on primary and secondary endpoints to help optimize patient selection. Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter Phase 3 trial. Primary endpoints were progression-free survival (PFS) and hepatic PFS (hPFS). Overall survival (OS) and time to deterioration of quality of life (TTDQOL) were secondary. Post-hoc analyses of the following subgroups were performed: Subgroup A (excluding patients with both ECOG=1 and CEA≥35ng/mL) and Subgroup B (patients with KRAS wild-type and either ECOG=0 or CEA&lt;35ng/mL). Kaplan-Meier analyses, hazard ratios (HRs) and log-rank tests were used to compare outcomes between TARE plus chemo and chemo only groups. Results: In Subgroup A, 160 (75.1%) patients were randomized to chemo only, versus 143 (66.5%) to the TARE arm. In Subgroup B, 91 (42.7%) patients were randomized to chemo only, versus 77 (35.8%) to the TARE arm. Results are shown for PFS, hPFS, OS, and TTDQOL in the intent-to-treat population. In both subgroups A and B, PFS, hPFS, and TTDQOL were significantly improved for the TARE plus chemo arm as compared to the chemo only arm; no OS difference was found. Conclusions: Careful patient selection using multiple prognostic factors is necessary to identify those who will benefit most from TARE with second-line chemo. Prognostic factors were important in identifying the level of benefit seen in patients treated with TARE and chemo versus chemo alone. Clinical trial information: NCT01483027 . [Table: see text]

Volumetric Enhancing Tumor Burden at CT to Predict Survival Outcomes in Patients with Neuroendocrine Liver Metastases after Intra-arterial Treatment

Purpose To investigate whether liver enhancing tumor burden (LETB) assessed at contrast-enhanced CT indicates early response and helps predict survival outcomes in patients with multifocal neuroendocrine liver metastases (NELM) after intra-arterial treatment. Materials and Methods This retrospective study included patients with NELM who underwent intra-arterial treatment with transarterial embolization (TAE) or chemoembolization (TACE) between April 2006 and December 2018. Tumor response in treated NELM was evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) and modified RECIST (mRECIST). LETB was measured as attenuation 2 SDs greater than that of a region of interest in the nontumoral liver parenchyma. Overall survival (OS); time to unTA(C)Eable progression, defined as the time from the initial treatment until the time when intra-arterial treatments were considered technically unfeasible, either not recommended by the multidisciplinary tumor board or until death; and hepatic and whole-body progression-free survival (PFS) were evaluated using multivariable Cox proportional hazards analyses, the Kaplan-Meier method, and log-rank test. Results The study included 119 patients (mean age, 60 years ± 11 [SD]; 61 men) who underwent 161 treatments. A median LETB change of -25.8% best discriminated OS (83 months in responders vs 51 months in nonresponders; P = .02) and whole-body PFS (18 vs 8 months, respectively; P < .001). A -10% LETB change best discriminated time to unTA(C)Eable progression (32 months in responders vs 12 months in nonresponders; P < .001) and hepatic PFS (18 vs 8 months, respectively; P < .001). LETB change remained independently associated with improved OS (hazard ratio [HR], 0.56), time to unTA(C)Eable progression (HR, 0.44), hepatic PFS (HR, 0.42), and whole-body PFS (HR, 0.47) on multivariable analysis. Neither RECIST nor mRECIST helped predict patient outcome. Conclusion Response according to LETB change helped predict survival outcomes in patients with NELM after intra-arterial treatments, with better discrimination than RECIST and mRECIST. Keywords: CT, Chemoembolization, Embolization, Abdomen/GI, Liver Supplemental material is available for this article. © RSNA, 2023.

Prognostic Factors for Effectiveness Outcomes After Transarterial Radioembolization in Metastatic Colorectal Cancer: Results From the Multicentre Observational Study CIRT

BackgroundTransarterial radioembolisation (TARE) with Yttrium-90 resin microspheres is a treatment option for patients with metastatic colorectal cancer in the liver (mCRC). A better understanding of the prognostic factors and treatment application can improve survival outcomes. MethodsWe analysed the safety and effectiveness of 237 mCRC patients included in the prospective observational study CIRSE Registry for SIR-Spheres Therapy (CIRT) for independent prognostic factors for overall survival (OS), progression-free survival (PFS) and hepatic progression-free survival (hPFS) using the Cox proportional-hazard model. ResultsThe median OS was 9.8 months, median PFS was 3.4 months and median hPFS was 4.2 months. Independent prognostic factors for an improved overall survival were the absence of extra-hepatic disease (P= .0391), prior locoregional procedures (P= .0037), an Aspartate transaminase to Platelet Ratio Index (APRI) value of ≤0.40 (P< .0001) and International Normalized Ratio (INR) ≤1 (P= .0078). Partition model dosimetry resulted in improved OS outcomes compared to the body surface area model (P = .0120). Independent predictors for PFS were APRI >0.40 (P = .0416) and prior ablation (P = .0323), and for hPFS these were 2 to 5 tumor nodules (P = .0148), Albumin-bilirubin (ALBI) grade 3 (P = .0075) and APRI >0.40 (P = .0207). During the study, 95 of 237 (40.1%) patients experienced 197 adverse events, with 28 of 237 (11.8%) patients having a grade 3 or higher adverse events. ConclusionIncluding easy-to-acquire laboratory markers INR, APRI, ALBI and using partition model dosimetry can identify mCRC patients that may benefit from TARE.

Addition of Y-90 radioembolization increases tumor response and local disease control in hepatocellular carcinoma patients receiving sorafenib

PurposeTo comparethe treatment response and progression-free survival (PFS) in advanced hepatocellular carcinoma (HCC) patients who received sorafenib treatment either alone or combined with radioembolization (RE).MethodsFollow-up images of the patients treated within a multicenter phase II trial (SORAMIC) were assessed by mRECIST. A total of 177 patients (73 combination arm [RE + sorafenib] and 104 sorafenib arm) were included in this post-hoc analysis. Response and progression characteristics were compared between treatment arms. Survival analyses were done to compare PFS and post-progression survival between treatment arms. Multivariate Cox regression analysis was used to compare survival with factors known to influence PFS in patients with HCC.ResultsThe combination arm had significantly higher objective response rate (61.6% vs. 29.8%, p < 0.001), complete response rate (13.7% vs. 3.8%, p = 0.022), and a trend for higher disease control rate (79.2% vs. 72.1%, p = 0.075). Progression was encountered in 116 (65.5%) patients and was more common in the sorafenib arm (75% vs. 52.0%, p = 0.001). PFS (median 8.9 vs. 5.4 months, p = 0.022) and hepatic PFS were significantly better in the combination arm (9.0 vs. 5.7 months, p = 0.014). Multivariate analysis confirmed the treatment arm as an independent predictor of PFS.ConclusionIn advanced HCC patients receiving sorafenib, combination with RE has an additive anticancer effect on sorafenib treatment resulting in a higher and longer tumor response. However, the enhanced response did not translate into prolonged survival. Better patient selection and superselective treatment could improve outcomes after combination therapy.

Isolated hepatic perfusion as a treatment for uveal melanoma liver metastases, first results from a phase III randomized controlled multicenter trial (the SCANDIUM trial).

LBA9509 Background: Uveal melanoma is the most common primary intraocular malignancy in adults. Despite successful control of the primary tumor, metastatic disease will ultimately develop in approximately 50% of the patients, with the liver being the most common site. The median survival for patients with liver metastases is about 6-12 months, and there are only few systemic treatment options available that moderately prolong survival. A previous trial using isolated hepatic perfusion (IHP) has suggested a 14-month increase in overall survival, compared with a historical control group consisting of the longest surviving patients in Sweden during the same time period (26 vs. 12 months). Methods: In this multicenter randomized, controlled, phase III trial, patients with previously untreated isolated liver metastasis from uveal melanoma were randomized between 2013 and 2021 to receive IHP or best alternative care (control group). The primary end point is overall survival at 24 months, but here we report the secondary outcomes of response according to RECIST 1.1 criteria, progression-free survival (PFS), hepatic PFS (hPFS) and toxicity. Results: A total of 93 patients were randomized, with three patients in each group being excluded due to either withdrawal of consent or inappropriate enrollment, and a total of 87 patients were assigned to either IHP group (43 patients) or control group (44 patients). In the IHP group, 41 (89%) patients were treated per protocol, and in the control group, 49% of the patients were treated with chemotherapy, 39% with immunotherapy and 9% with localized treatment interventions. In an intention-to-treat analysis, the overall response rate (ORR) in the IHP group was 40% (17/43) compared to 4.5% (2/44) in the control group (p&lt;0.0001). The median hPFS in the IHP group was 9.1 months (95% CI, 5.6 to 13.4 months), compared to 3.3 months (95% CI, 2.9 to 4.0 months) in the control group (p&lt;0.0001). The median PFS in the IHP group was 7.4 months (95% CI, 5.2 to 11.6 months), compared to 3.3 months (95% CI, 2.9 to 3.7 months) in the control group (p&lt;0.0001). There were 14 treatment-related serious adverse events in the IHP group, where vascular complication and infections were the most common side effects, compared to 13 in the control group where immunotherapy related side effects were most common. There was one treatment related death in the IHP group. Conclusions: Treatment with IHP resulted in superior ORR, hPFS and PFS compared to best alternative care among previously untreated patients with isolated uveal melanoma liver metastasis. Clinical trial information: NCT01785316.

Selective internal radioembolization (SIRT) allows to control liver metastases of gastrointestinal stromal tumors (GIST) failing treatment with tyrosine kinase inhibitors (TKI).

11540 Background: The liver and the peritoneum are the main area of metastatic spread in GIST. Liver resection does not play a role for hepatic metastases in comparison to f.e. colorectal cancer. If hepatic metastases are the only or major area of tumor progression and are resistant to available TKIs due to a missing mutation in KIT/PDGFRA/SDH (‘wildtype’) or after treatment with 1st/2nd/3rd/4th line therapy, interventional radioembolization with yttrium-90 (90Y) microspheres are promising treatment options, as radiation doses as high as 200Gy can be applied locally. We analyzed the long-term results of SIRT with respect to hepatic-progression-free survival (HEP-PFS) in a consecutive cohort of patients Methods: From 1/2008 to 1/2018, 2^6 pts (12f, 14m) with biopsy proven liver metastases of GIST which were the only (n = 13) or the dominant site of progression (n = 12) were treated by SIRT. Median age at GIST diagnosis had been 51.8 yrs and when receiving SIRT was 57.6yrs (range, 18–75yrs). The mutational status was ‘wildtype’ (n = 7, 2 NF-1), exon 11 (n = 7), exon 11+2nd mutation (n = 7), exon 9 (n = 3), exon 9+2ndmut (n = 1), and, exon 13 (n = 1). All patients except of two had prior TKI therapy: 1 line n = 3, 2 lines n = 11, 3-4 lines n = 9. Follow-up after SIRT was done via dynamic MRI and contrast-enhanced (CE)-CT, the median follow-up is 33.6 mos (range, 12-108mos) and all patients were followed until death Results:.The median hepatic-progression free survival (HEP-PFS) after SIRT was 17 months (range, 5-53+, 95%CI 10.7-23.8 mos). Of the patients with concomitant extrahepatic disease, the extraHEP-PFS was median 10 months. Twelve patients received next-line TKI therapy for progressive extrahepatic disease, whereas six patients required this for progressive liver metastases. When comparing the results according to the mutational status, patients with a ‘wildtype’ tumor showed a better median HEP-PFS of 19 mos (range, 12-53+, 95%CI 16.7-21.2 mos.) in comparison to KIT exon 9/11/13 mutated patients with only 14 months (range, 4-34 mos., 95%CI 6.5-21.4 mos), p &lt; 0.11 (Wilcoxon). Conclusions: 90Y radioembolization (SIRT) offers a safe and effective treatment for patients with liver metastases of GISTs being the dominant site of tumor progression and with no drug treatment options available. In patients known to have no mutation in KIT/PDGFRA (wt, also NF-1 associated) it looks whether the results might be even more promising and SIRT could be used in earlier treatment lines.

P-17 Real-life use and long-term effectiveness results from CIREL – the multi-centre, observational study on irinotecan-eluting transarterial chemoembolization in CRLM

Transarterial chemoembolization (TACE) using irinotecan-eluting beads as a treatment approach for patients with unresectable colorectal cancer liver metastases (CRLM) is finding use beyond treatment guidelines but real-life data from multi-centre studies are lacking. The CIrse REgistry for LifePearl microspheres (CIREL, NCT03086096) is a prospective, Europe-wide, multi-centre, observational study on the real-life clinical outcomes of LifePearlTM microspheres TACE (LP-irinotecan TACE). The study was conducted by the Cardiovascular and Interventional Radiological Society of Europe (CIRSE). Eligible patients were adults with CRLM treated with LP-irinotecan TACE and were enrolled between February 2018 and August 2020. Baseline characteristics and treatment-related data were collected. The median follow-up inclusion according to reverse Kaplan-Meier was 19 months (95% CI: 17-23) during which data on overall survival (OS), progression-free survival (PFS), hepatic progression free survival (hPFS) and adverse events (AEs) graded according to CTCAE 4.03 were collected. 152 patients were enrolled in the study. Median age was 66 years and 39% were female. Eastern Cooperative Oncology Group was 0 in 59%; 1 in 34%; and ≥2 7%; liver involvement was 50% in 7% of patients. 84% had progressive disease at baseline. 42% received 1 line, 40% 2 or more lines and 18% no line of previous systemic therapy. 91 (60%) patients experienced 266 adverse events within 24 hours after a TACE session, of which 19 (7%) were grade 3 or higher in 12 (8%) patients. The complete treatment plan was administered in 80% of patients and no treatment-related deaths were reported. The median OS for the whole cohort was 13.0 months (95% CI 10.5-15.0), median hPFS was 6.2 months (95% CI 5.1-6.9) (hPFS rate at 9 months: 29%) and median PFS was 4.7 months (95% CI 3.8-5.3) (PFS rate at 9 months: 13%). We could observe statistically significant differences (p=0.005) in OS for different treatment strategies. When LP-irinotecan TACE was used as a first-line treatment or as consolidation after response to first-line treatment (41, 27%), the median OS was 17 months (95% CI 12.7-23.1). When it was used in combination with ablation (with curative intent) (19, 13%), the median OS was 17.1 (95% CI 10.5-NA). When chemo-refractory patients still eligible for further systemic treatment were treated with LP-irinotecan TACE (41, 27%), the median OS was 10.3 months (95% CI 7.5-14.0). Salvage treatment of chemo-refractory patients not eligible for further systemic treatment (46, 30%) resulted in the smallest median OS of 9.0 months (95% CI 6.8-13.0). For 5 (3%) patients LP-irinotecan TACE was used after response to second-line treatment. The results from this large prospective multi-centre observational study show that in a real-world context, LP-irinotecan TACE is well tolerated with low occurrences of severe adverse events and patients with CRLM receiving LP-irinotecan have a median overall survival comparable to gold-standard systemic treatment for later lines.