Hepatic Progression-free Survival Research Articles

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<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.

Hepatic arterial infusion pump chemotherapy combined with systemic therapy for patients with advanced colorectal liver metastases: Outcomes in a newly established program.

Colorectal liver metastasis (CRLM) is a leading cause of morbidity and mortality in patients with colorectal cancer. Hepatic arterial infusion (HAI) chemotherapy has been demonstrated to improve survival in patients with resected CRLM and to facilitate conversion of technically unresectable disease. Between 2016 and 2018, n = 22 HAI pumps were placed for CRLM. All patients received systemic chemotherapy concurrently with HAI floxuridine/dexamethasone. Overallsurvival(OS) and progression-free survival (PFS) were assessed using the Kaplan-Meier method. HAI pumps were placed in seven patients with completely resected CRLM and 15 patients with unresectable disease. Twenty-one patients received HAI floxuridine with a median of 5 total HAI cycles (interquartile range: 4-7). Biliary sclerosis was the most common HAI-related complication (n = 5, 24%). Of the 13 patients treated to convert unresectable CRLM, 3 (23%) underwent hepatic resection with curative intent after a median of 7 HAI cycles (range: 4-10). For all HAI patients, the mean OS was 26.7 months from CRLM diagnosis, while the median PFS and hepatic PFS from pump placement were 9 and 13 months, respectively. Concomitant HAI and systemic therapy can be utilized at multidisciplinary programs for patients with advanced CRLM, both in the adjuvant setting and to facilitate conversion of unresectable disease.

The comparison of local tumor control after microwave ablation, surgical resection and combined treatment for colorectal liver metastases

Aim. We aimed to compare the local therapeutic efficiency of microwave ablation (MWA), surgical resection, and combined treatment, assess the outcomes, and identify predictive factors for local treatment response in colorectal liver metastases (CLMs). Methods. From March 2013 to September 2019, a total of 54 patients with 302 CLMs were enrolled in this retrospective study. Eleven patients (20.4%) were treated with MWA, 9 patients (16.7%) with surgery, and 34 patients (63%) with the combined method. Univariate and multivariate analyses were performed to investigate overall survival (OS) and hepatic progression-free survival (HPFS) using the Cox proportional hazard regression model. The logistic regression analysis was used to identify the predictive factors for the local treatment response. Results. Total treatment response was achieved in 46.3% (n=25) of the patients. Local tumor progression was seen in 7.4% (n=4) of the patients, and the rate of intrahepatic distal recurrence was 46.3% (n=25). There were no significant differences in HPFS and OS between the three groups (p=0.56 and 0.90, respectively). Younger age (&lt;60), smaller (≤ 2 cm) or fewer (≤3) liver metastases, and wild-type RAS were predictive for higher rates of local treatment response (OR 0.22, 95% CI 0.15-0.93, p=0.04; OR 1.12, 95% CI 0.54-2.12, p=0.029; OR 1.37, 95% CI 0.97-2.37, p=0.035; OR 0.23, 95% CI 0.10-0.85, p=0.028, respectively). Conclusions. The results of this study reveal that the use of MWA, alone or combined with resection, may achieve high local treatment response and similar survival rates compared to patients undergoing resection, suggesting that MWA could potentially be preferred over surgical procedures.

Radioembolization with chemotherapy for liver-dominant colorectal cancer: Analysis of patient subgroups in the EPOCH trial.

115 Background: The EPOCH trial evaluated potential benefit of second-line transarterial radioembolization (TARE) plus chemotherapy compared to chemotherapy alone in patients with liver-dominant metastatic colorectal disease (mCRC). Presented here are additional results from EPOCH of depth and duration of response (DoR), and progression-free survival (PFS) and hepatic progression-free survival (hPFS) subgroup analyses. Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter phase 3 trial of second-line chemotherapy for liver-dominant mCRC comparing outcomes from chemotherapy with or without unilobar or same-day bilobar TARE treatment using glass microspheres. Primary study endpoints were PFS and hPFS. Pre-specified subgroup analyses of PFS and hPFS were performed. PFS, hPFS, DoR for patients with objective response, and depth of response (percent change from baseline to nadir in sum of longest diameters of target lesions) were based on blinded, independent central review using RECIST 1.1. The use of TheraSphere in the trial in the USA was under Investigational Device Exemption from FDA. Results: Both primary endpoints of PFS (HR = 0.69, 95% CI: 0.54, 0.88; 1-sided p=0.0013) and hPFS (HR = 0.59, 95% CI: 0.46, 0.77; 1-sided p&lt;0.0001) were met in the EPOCH study. Median DoR in the 73 responders of the TARE arm was numerically longer, with 7.2 months by Kaplan-Meier analysis; in the 45 responders of the chemotherapy only arm, 6.6 months (HR = 0.79, 95% CI: 0.48, 1.30; 1-sided p = 0.178). Mean depth of response across all patients in the TARE arm with data available (N=196) was -25.6%, compared to -13.0% in the chemotherapy only arm (N=182; mean difference -12.6 percentage points; 95% CI: -18.9, -6.3; 1-sided p = 0.0001). Key subgroups of interest which showed improved PFS and/or hPFS in the TARE arm (ie, 95% CI for the HR entirely below 1) are as follows: Conclusions: These data suggest that liver-dominant mCRC patients in this trial benefitted in second-line treatment from a combination of TARE plus chemotherapy based upon improved PFS and hPFS over the full set of patients and in a number of subgroups. The addition of TARE to chemotherapy improves depth of response compared to chemotherapy alone. Clinical trial information: NCT01483027. [Table: see text]

Perioperative and oncologic outcomes of hepatic artery infusion pump therapy at an expanding HAI program.

120 Background: Hepatic artery infusion (HAI) is a liver directed therapy to treat unresectable or resected colorectal liver metastases (CRLM) and unresectable intrahepatic cholangiocarcinoma (ICC). Historically, HAI has only been performed at few specialized centers; however, there is increasing expansion to new centers. We previously reported safety outcomes of our index year of HAI therapy. We now report safety, feasibility, efficacy and oncologic outcomes for an expanded cohort of 62 patients in an established HAI program. Methods: Patients selected for HAI by multidisciplinary review were evaluated for demographics and perioperative outcomes. Objective hepatic response was calculated according to RECIST 1.1. Overall, hepatic and extrahepatic progression-free survival (PFS) were calculated by the Kaplan-Meier method on an intent-to-treat basis. Results: 62 patients were treated with HAI from November 2018-September 2021: 46 for unresectable CRLM, 8 as adjuvant HAI for resected CRLM, and 8 for unresectable ICC. Median age was 54.5 years (range 32-80), 58% were male, and 97% received prior chemotherapy (median 12 cycles, range 0-66). Hepatectomy (18, 29%) and/or colectomy/proctectomy (27, 43.5%) was performed concurrently with pump placement, and 19 (30.6%) were performed robotically. Median operating time was 265 minutes (range 130-526), estimated blood loss was 100 mL (range 22-1000) and length of stay was 5 days (range 1-19). HAI-specific complications occurred in 14% (Table). Floxuridine (FUDR) was initiated in 95% of patients a median of 18.5 days after surgery. Of the 38 patients who received HAI for unresectable CRLM and had measurable disease on imaging, 3- and 6-month hepatic disease control was achieved in 86% (8 partial response [PR], 22 stable disease [SD], 5 progressed [PD]) and 89% (1 complete response, 8 PR, 8 SD, 2 PD), respectively. For patients with at least 3 months follow-up, median PFS, hepatic PFS and extrahepatic PFS were 13 months, 13 months, and 13 months, respectively. Conclusions: HAI can be safely and effectively delivered to well-selected patients with CRLM and ICC. Response rates, disease control and PFS in heavily treated patients with unresectable CRLM comparable to high-volume centers can be achieved at new programs with appropriate expertise. These data support the mission of the newly formed HAI Consortium to critically evaluate efficacy and innovation in HAI therapy through multi-institutional collaboration and contemporary prospective trials.[Table: see text]

Radioembolization with chemotherapy for liver-dominant colorectal cancer: Time to subsequent treatment and quality of life in the EPOCH trial.

114 Background: The primary objective of the EPOCH trial evaluated potential benefit of adding second-line transarterial radioembolization (TARE) with yttrium-90 glass microspheres to chemotherapy compared to chemotherapy alone in patients with liver-dominant metastatic colorectal disease (mCRC). Secondary endpoints included time to deterioration of quality of life (TTDQoL). Methods: EPOCH was a 1:1 randomized, open-label, global, multicenter phase 3 trial. TTDQoL was assessed using the Functional Assessment of Cancer Therapy-colorectal (FACT-c) questionnaire and defined as the time from randomization to the change from baseline in FACT-c total score ≤ -7 points or date of death and was estimated using Kaplan-Meier analysis. Time to subsequent therapy was defined as the time from randomization to the start of subsequent therapy and was estimated using Kaplan-Meier analysis. Restricted mean survival time (RMST) analysis was used to estimate the area under Kaplan-Meier curves (AUC) for progression-free survival (PFS), hepatic PFS (hPFS), and TTDQoL, and the difference in AUC estimates between the two arms were assessed. The use of TheraSphere in the USA in the trial was under Investigational Device Exemption from FDA. Results: The EPOCH trial included 428 patients. Both primary endpoints of PFS (HR = 0.69, 95% CI: 0.54, 0.88; 1-sided p=0.0013) and hPFS (HR = 0.59, 95% CI: 0.46, 0.77; 1-sided p&lt;0.0001) were met in the EPOCH study. Median time to subsequent therapy in the TARE plus chemotherapy arm was 21.0 months, compared to 10.1 months in the chemotherapy only arm (HR = 0.49, 95% CI: 0.37, 0.67). TTDQoL before subsequent therapy was reported in 53.5% (115/215) patients in the TARE plus chemotherapy arm, compared to 43.7% of patients in the chemotherapy only arm (93/213). Median TTDQoL was 3.8 months in both the TARE plus chemotherapy arm and the chemotherapy alone arm (1-sided p=0.1513; HR = 0.86, 95% CI: 0.65, 1.14). AUC for PFS until 22.1 months was 9.4 months (95% CI: 8.4, 10.4) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.6, 8.1) for the chemotherapy only arm (1-sided p=0.0008). AUC for hPFS until 22.1 months was 10.3 months (95% CI: 9.2, 11.3) for the TARE plus chemotherapy arm, compared to 7.4 months (95% CI: 6.7, 8.2) for the chemotherapy only arm (1-sided p&lt;0.0001). AUC for TTDQoL until 18.5 months was 6.6 (95% CI: 5.6, 7.6) for the TARE plus chemotherapy arm, compared to 5.5 (95% CI: 4.4, 6.5) for the chemotherapy only arm (1-sided p=0.0663). Conclusions: These results suggest that the addition of TARE to second-line chemotherapy in patients with liver-dominant mCRC extended PFS, hPFS, and time to subsequent treatment without compromising quality of life. Clinical trial information: NCT01483027.

Prospective evaluation of percutaneous hepatic perfusion with melphalan as a treatment for unresectable liver metastases from colorectal cancer.

Percutaneous hepatic perfusion with melphalan (M-PHP) is increasingly used in patients with liver metastases from various primary tumors, yet data on colorectal liver metastases (CRLM) are limited. The aim of this study was to prospectively evaluate the efficacy and safety of M-PHP in patients with CRLM. Prospective, single-center, single-arm phase II study of M-PHP with hemofiltration in patients with unresectable CRLM. Proven, extrahepatic metastatic disease was one of the exclusion criteria. Primary outcomes were overall response rate (ORR) and best overall response (BOR). Secondary outcomes were overall survival (OS), progression-free survival (PFS), hepatic PFS (hPFS), and safety. A total of 14 M-PHP procedures were performed in eight patients between March 2014 and December 2015. All patients (median age 56 years, ranging from 46 to 68) had received (extensive) systemic chemotherapy before entering the study. The ORR was 25.0%, with two out of eight patients showing partial response as BOR. Median OS was 17.3 months (ranging from 2.6 to 30.9) with a one-year OS of 50.0%. Median PFS and hPFS were 4.4 and 4.5 months, respectively. No serious adverse events occurred. Grade 3/4 hematologic adverse events were observed in the majority of patients, though all were transient and well-manageable. M-PHP is a safe procedure with only limited efficacy in patients with unresectable CRLM who already showed progression of disease after receiving one or more systemic treatment regimens.

Selective internal radiation therapy for hepatic metastases of uveal melanoma: a systematic review.

Uveal melanoma (UM) commonly metastasizes to the liver. Treatment usually consists of liver-directed therapies, such as selective internal radiation therapy (SIRT). This review aimed to assess the effectiveness and safety of SIRT for hepatic metastases from UM. The study protocol is available at OSF (https://osf.io/vhyct/). EMBASE and MEDLINE were searched until July 2020, using terms related to SIRT and hepatic metastases from UM. Studies reporting outcomes of SIRT in patients with UM and at least one hepatic metastasis were included. Data on overall survival (OS), hepatic progression free survival (hPFS) or tumor response were collected. The Newcastle-Ottawa Scale (NOS) was used to assess risk of bias. 11 studies were included, reporting outcomes for 268 patients with hepatic metastases from UM. Most studies (n = 9, 81.8%) were retrospective. Disease control was achieved in 170 patients (67.5%) and the median OS from time of SIRT was 12.3 months. Median hPFS was 5.4 months. Low-grade side-effects were common but serious complications were infrequent. There were two treatment-related deaths. The median NOS score was 6 (moderate risk of bias). SIRT appears to be a safe and effective treatment for patients with unresectable hepatic metastases from UM. The certainty of our results is unclear due to predominantly retrospective data with moderate risk of bias. Further prospective studies are required to explore the role of SIRT in UM. SIRT appears to be a safe treatment for patients with unresectable hepatic metastases from UM. Further prospective work is required.

Transarterial Yttrium-90 Glass Microsphere Radioembolization of Chemotherapy-Refractory Breast Cancer Liver Metastases: Results of a Single Institution Retrospective Study

PurposeOur purpose was to retrospectively evaluate the safety and efficacy of transarterial hepatic radioembolization (TARE) treatment with yttrium-90 labeled glass microspheres in patients with chemotherapy-refractory breast cancer with liver-dominant metastatic disease. Methods and MaterialsThis retrospective single-institution study evaluated 31 female patients (mean age of 59.6 ± 13.2 years) who were treated with TARE. All patients received and progressed on systemic chemotherapy before TARE. Twenty-one patients also had extrahepatic metastases, including 13 patients who had metastases in bones only besides the liver. Survival data were analyzed by Kaplan-Meier method and compared using log-rank test. Imaging response to treatment was determined by Response Evaluation Criteria in Solid Tumors. ResultsMedian overall survival (OS) from the TARE was 13 months (95% confidence interval, 9.1-16.9 months). The survival probability at 1, 2, and 3 years was 60.1%, 36.7%, and 24.5%, respectively. The median hepatic progression-free survival was 7 months (95% confidence interval, 6.1-7.9 months). There was no 30-day mortality and 3 patients (9.4%) had grade 3 toxicity. Estrogen receptor (ER) positive status predicted prolonged survival (14 months for ER+ vs 9 months for ER-; P = .028). Patients who had bone-only extrahepatic disease had higher OS than patients with extraosseous metastases (23 vs 8 months, P = .02). At the 3-month follow-up the radiographic objective response rate was 46.6% and disease control rate was 70%. ConclusionsThe treatment of patients with liver-dominant chemotherapy-refractory breast cancer metastases with TARE using yttrium-90 labeled glass microspheres is safe and led to promising hepatic disease control and OS especially in patients with ER+ tumors and in patients without extrahepatic extraosseous metastases.

Salvage regional therapy using hepatic artery infusion pump in unresectable chemotherapy resistant colorectal liver metastases

BackgroundLittle is known about the influence of hepatic artery infusion pump (HAIP) therapy in the setting of chemotherapy resistant hepatic disease in the era of modern systemic therapies. MethodsPatients who underwent HAIP therapy for chemotherapy resistant and unresectable colorectal liver metastases (CRLM) were reviewed retrospectively. ResultsA total of 25 patients met inclusion criteria. 52% had isolated CRLM and 92% had five or more metastatic lesions. Partial response was noted in 40% of patients. Median hepatic progression-free survival (PFS) was 7 months in those with extrahepatic disease versus 6 months in those with isolated CRLM at the time of HAIP placement (p = 0.75). Median overall survival was 8 months in patients with extrahepatic disease and 14 months in patients with isolated CRLM (p = 0.06). ConclusionsOur findings are comparable to published data and augment the literature which supports HAIP use in chemotherapy-resistant, liver-predominant metastatic colorectal cancer patients.

Meta-Analysis of Isolated Hepatic Perfusion and Percutaneous Hepatic Perfusion as a Treatment for Uveal Melanoma Liver Metastases.

Simple SummaryIsolated hepatic perfusion is one of the available treatment options for patients with liver metastases from uveal melanoma. This is an open surgical procedure where the liver is isolated from the circulation and perfused with a chemotherapeutic agent. A modern development is the minimally invasive percutaneous hepatic perfusion, where the liver is endovascularly isolated and then perfused with a chemotherapeutic agent through a catheter in the arterial system. Within this systematic review and meta-analysis, we aim to compare these modalities in terms of overall survival, progression-free survival, complications and response.Background: Uveal melanoma is the most commonly occurring primary intraocular malignancy in adults, and patients have a high risk of developing metastatic disease, mostly in the liver. Isolated hepatic perfusion (IHP) with melphalan is a liver-directed therapy for patients with liver metastases. Percutaneous hepatic perfusion (PHP), a minimally invasive technique, is available as well. PHP benefits from the fact that the procedure can be repeated and therefore possibly offers better survival. We conducted a systematic review and meta-analysis comparing both techniques. Methods: A systematic literature search was performed using the electronic databases of Scopus, MEDLINE, Web of Science, PubMed and Cochrane CENTRAL. A total of nine articles reporting on eight studies were included in the analysis. Individual survival data were extracted from each study. Results: The median overall survival (OS) was 17.1 months for IHP and 17.3 months for PHP. The median progression-free survival (PFS) was 7.2 months for IHP and 9.6 months for PHP. The median hepatic progression-free survival was 10 months for IHP and 9.5 months for PHP. The complication rate and 30-day mortality rate were 39.1% and 5.5% for IHP and 23.8% and 1.8% for PHP. Conclusion: There was no difference in OS or PFS between IHP and PHP for patients with uveal melanoma liver metastases, but patients have significantly less of a risk for complications and mortality following PHP.

Initiation of Chemosaturation With Percutaneous Hepatic Perfusion Program in Interventional Radiology Department.

ObjectivesChemosaturation with percutaneous hepatic perfusion (PHP) is a relatively new minimally-invasive liver-directed therapy, which aims to deliver high-dose chemotherapy into the liver with low systemic side effects. Initial studies showed promising results, especially in the treatment of metastatic uveal melanoma. But unfamiliarity of the interventional radiologists prevents its widespread implantation in clinical routine. This study aimed to outline how to initiate a PHP program and report initial results.MethodsWe retrospectively reviewed all patients who underwent chemosaturation with PHP in our institution between March 2016 and February 2017 and their follow-up results till October 2018. Patient demographics, procedural characteristics, clinical and imaging results, and complications were evaluated. Additionally, modifications regarding infrastructure and procedure techniques were described.ResultsA total of three patients (two females and one male) with a mean age of 59 underwent six PHP procedures. The primary disease was colorectal carcinoma in one patient and uveal melanoma in two patients. The technical success rate was 100% and the mean melphalan dose was 190.8 mg. No procedural death was observed. Patients were hospitalized for a mean of 3.3 days after procedures. Grade 3 and 4 complications were seen after 50% and 33.3% of procedures, respectively. Two patients showed partial response and the other patient showed stable disease after procedures. Mean hepatic progression-free survival was 10.8 months. Overall survival from the first procedure was 14.8 months in our cohort.ConclusionOur results show that chemosaturation with PHP offers a promising minimally invasive treatment option in patients with unresectable liver metastases. The technical challenges of PHP can be easily handled by an experienced interventional radiology (IR) team. It is a relatively safe procedure and its toxicities are usually hematological and can be manageable with close surveillance and appropriate medical therapies.

Yttrium-90 Hepatic Radioembolization for Advanced Chemorefractory Metastatic Colorectal Cancer: Survival Outcomes Based on Right- Versus Left-Sided Primary Tumor Location.

BACKGROUND. Primary colon cancer location affects survival of patients with metastatic colorectal cancer (mCRC). Outcomes based on primary tumor location after salvage hepatic radioembolization with 90Y resin microspheres are not well studied. OBJECTIVE. The objectives of this study are to assess the survival outcomes of patients with advanced chemorefractory mCRC treated with 90Y radioembolization, as stratified by primary tumor location, and to explore potential factors that are predictive of survival. METHODS. A total of 99 patients who had progressive mCRC liver metastases while receiving systemic therapy and who were treated with 90Y radioembolization at a single center were retrospectively analyzed. For 89 patients, tumor response on the first imaging follow-up examination (CT or MRI performed at a mean [± SD] of 1.9 ± 0.9 months after 90Y radioembolization) was evaluated using RECIST. Overall survival (OS), OS after 90Y radioembolization, and hepatic progression-free survival (PFS) were calculated using the Kaplan-Meier method. Outcomes and associations of outcomes with tumor response were compared between patients with left- and right-sided tumors. RESULTS. A total of 74 patients had left-sided colon cancer, and 25 patients had right-sided colon cancer. Median OS from the time of mCRC diagnosis was 37.2 months, median OS after 90Y radioembolization was 5.8 months, and median hepatic PFS was 3.3 months. Based on RECIST, progressive disease on first imaging follow-up was observed in 38 patients (43%) after 90Y radioembolization and was associated with shorter OS after 90Y radioembolization compared with observation of disease control on first imaging follow-up (4.0 vs 10.5 months; p < .001). Patients with right-sided primary tumors showed decreased median OS after 90Y radioembolization compared with patients with left-sided primary tumors (5.4 vs 6.2 months; p = .03). Right- and left-sided primary tumors showed no significant difference in RECIST tumor response, hepatic PFS, or extrahepatic disease progression (p > .05). Median survival after 90Y radioembolization was significantly lower among patients with progressive disease than among those with disease control in the group with left-sided primary tumors (4.2 vs 13.9 months; p < .001); however, this finding was not observed in the group with right-sided primary tumors (3.3 vs 7.2 months; p = .05). CONCLUSION. Right-sided primary tumors were independently associated with decreased survival among patients with chemorefractory mCRC after 90Y radioembolization, despite these patients having a similar RECIST tumor response, hepatic PFS, and extrahepatic disease progression compared with patients with left-sided primary tumors. CLINICAL IMPACT. Primary colon cancer location impacts outcomes after salvage 90Y radioembolization and may help guide patient selection.

68Ga-DOTATATE PET/CT and MRI with Diffusion-Weighted Imaging (DWI) in Short- and Long-Term Assessment of Tumor Response of Neuroendocrine Liver Metastases (NELM) Following Transarterial Radioembolization (TARE).

Simple SummaryTARE with 90Yttrium has become a valuable treatment option for patients with unresectable NELMs. However, early evaluation of therapy response remains challenging as size-based response assessments (such as RECIST) are known to be limited, especially in slow-growing tumors. Alternatives such as quantitative evaluation of SUV of 68Ga-DOTATATE PET/CT and ADC of DWI-MRI have not been compared so far. We found that early percentage changes in SUV tumor-to-organ ratios on first follow-up after TARE could predict longer HPFS in patients with NELM and were superior to ΔSUVmax/SUVmean alone or to ΔADC.The aim of this study was to evaluate the role of SUV and ADC in assessing early response in patients with NELM following TARE. Thirty-two patients with pre- and postinterventional MRI with DWI and 68Ga-DOTATATE PET/CT were included. ADC and SUV of three target lesions and of tumor-free spleen and liver tissue were determined on baseline and first follow-up imaging, and tumor to spleen (T/S) and tumor to liver (T/L) ratios were calculated. Response was assessed by RECIST 1.1 and mRECIST on first follow-up, and long-term response was defined as hepatic progression-free survival (HPFS) over 6, 12, and <24 months. In responders, intralesional ADC values increased and SUV decreased significantly regardless of standard of reference for response assessment (mRECIST/RECIST/HPFS > 6/12/24 m). Using ROC analysis, ΔSUV T/S ratio (max/max) and ΔSUV T/L ratio (max/mean) were found to be the best and most robust metrics to correlate with longer HPFS and were superior to ΔADC. ΔT/S ratio (max/max) < 23% was identified as an optimal cut-off to discriminate patients with longer HPFS (30.2 m vs. 13.4 m; p = 0.0002). In conclusion, early percentage changes in SUV tumor-to-organ ratios on first follow-up seem to represent a prognostic marker for longer HPFS and may help in assessing therapeutic strategies.