Median Liver Progression-free Survival Research Articles

Exploring a Novel Technique to Tackle the Shortage of Devices for Hepatic Arterial Infusion Chemotherapy: Early Results of an Alternate Approach for Percutaneous Arterial Port Catheter Placement.

Dedicated catheters for hepatic arterial infusion chemotherapy were removed from the market. The purpose of this study was to assess the results of a novel approach to overcome the shortage of dedicated catheters for hepatic arterial infusion chemotherapy in the treatment of colorectal cancer liver metastases. We retrospectively included patients who underwent a percutaneous placement of a hepatic intra-arterial port catheter in a single tertiary center from February 2021 to June 2022. We examined the patient baseline characteristics, technical features of the modified procedures, technical success rates, complications and oncological outcomes. Fourteen patients (median age: 60 years; q1 = 54; q3 = 70; range: 53-81 years) underwent 15 modified procedures. The main modification of our placement technique consisted of the use of an indwelling 5-Fr Vertebral catheter, on the tip of which we created a two-sided additional lateral hole. The catheter was connected to a pediatric port. The primary success rate was 100%, and the secondary success rate was 93.3%. There were two late major complications, graded IIIa according to the Clavien-Dindo classification. The median liver progression free survival was 6.1 months (q1 = 2.5; q3 = 7.2; range: 1.3-11.6). Our experience suggests that the derived utilization of the devices used routinely in interventional radiology provides an effective solution that can compensate for the shortage of dedicated devices.

HAIC as a potential therapy for esophageal cancer patients with liver metastasis: a retrospective cohort study.

This was a single-arm historical cohort study of ESCC patients with synchronous or heterochronous LM between December 2014 and July 2021 at the Department of Gastrointestinal Oncology. The patients were treated with HAIC for LM, and regular image assessments were performed according to the judgment of the interventional physician. Liver progression-free survival (PFS), liver objective response rate (ORR), liver disease control rate (DCR), overall survival (OS), adverse events (AEs), treatment information, and basic characteristics were observed retrospectively. Overall, a total of 33 patients were enrolled in this study. All included patients received catheterized HAIC therapy, with a median of three (ranging from 2 to 6) sessions. The treatment response of liver metastatic lesions included partial response (PR) in 16 (48.5%) patients, stable disease (SD) in 15 (45.5%) patients, and progressive disease (PD) in two (6.1%) patients, for an ORR of 48.5% and a DCR of 93.9%. The median liver PFS was 4.8 months (95% confidence interval (CI): 3.0-6.6 months), and the median OS was 6.4 months (95% CI: 6.1-6.6 months). Patients who achieved PR at the liver metastasis site after HAIC were more likely to have a longer OS than those who achieved SD or PD. Grade 3 AEs occurred in 12 patients. The most common grade 3 AE was nausea, occurring in 10 (30.0%) patients, followed by abdominal pain in three (9.1%) patients. Only one patient showed grade 3 elevation of alanine aminotransferase (ALT)/aspartate aminotransferase (AST), and one patient suffered from grade 3 embolism syndrome AEs. Grade 4 adverse events, followed by abdominal pain, occurred in one patient. Hepatic arterial infusion chemotherapy might be an option as a regional therapy for ESCC patients with LM, as it is acceptable and tolerable.

Yttrium-90 Radioembolization for Liver-Dominant Metastatic Prostate Cancer: A Case Series

Transarterial radioembolization (TARE) with yttrium-90 glass microspheres is widely used to treat primary and secondary malignancies in the liver. However, the safety and efficacy of TARE in patients with liver-dominant metastatic castration-resistant prostate cancer (mCRPC) is unknown. A proof-of-concept, retrospective analysis of 7 consecutive patients with liver-dominant mCRPC who were treated with TARE was performed. The median overall survival was 27.2, 32.1, and 108.1 months from the time of TARE, the diagnosis of liver metastases, and initial cancer diagnosis, respectively. The median liver progression-free survival was 7.3 months. No grade 3 or higher adverse effects were noted. TARE was found to be a safe and effective tool for treating patients with liver-dominant mCRPC in this limited cohort.

Predictive Parameters in Patients Undergoing Percutaneous Hepatic Perfusion with Melphalan for Unresectable Liver Metastases from Uveal Melanoma: A Retrospective Pooled Analysis

PurposeThe aim of this study was to identify positive predictors for survival in uveal melanoma (UM) patients treated with percutaneous hepatic perfusion with melphalan (M-PHP), by retrospectively pooling data from three centers.Materials and MethodsRetrospective analysis including patients (ge 18 years) treated with M-PHP between February 2014 and December 2019 for unresectable liver-dominant or liver-only metastases from UM. Predictors for OS were assessed using uni- and multivariate analyses. Other study outcome measures were response rate, progression-free survival (PFS), liver progression-free survival (LPFS), overall survival (OS) and complications according to CTCAEv5.0.ResultsIn total, 101 patients (47.5% males; median age 59.0 years) completed a minimum of one M-PHP. At a median follow-up time of 15.0 months, complete response (CR), partial response (PR), stable disease (SD) and progressive disease were seen in five (5.0%), 55 (54.5%), 30 (29.7%) and 11 (10.9%) patients, respectively, leading to a 89.1% disease control rate. Median PFS, LPFS and OS were 9.0, 11.0 and 20.0 months, respectively. Survival analyses stratified for radiological response demonstrated significant improved survival in patients with CR or PR and SD category. Treatment of the primary tumor with radiotherapy, ≥ 2 M-PHP and lactate dehydrogenase (LDH) < 248 U/L were correlated with improved OS. Thirty-day mortality was 1.1% (n = 2). Most common complication was hematological toxicity (self-limiting in most cases).ConclusionM-PHP is safe and effective in patients with UM liver metastases. Achieving CR, PR or SD is associated with improved survival. Primary tumor treatment with radiotherapy, normal baseline LDH and > 1 M-PHP cycles are associated with improved OS.

Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas.

Simple SummarySarcomas of the liver are a rare and aggressive group of malignancies for which surgery is the preferred treatment modality even though most patients are not surgical candidates and receive chemotherapy with poor outcomes. In these cases, trans-arterial liver-directed therapies are emerging as a new treatment option. Among these, radioembolization is a promising but understudied treatment option. In radioembolization, microbeads conjugated to a radioactive drug are injected into the blood vessels, nourishing the cancers and leading to cell death and tumor shrinkage. In this study, we retrospectively analyzed 35 patients with liver sarcomas receiving radioembolization at our institution. We found that those with disease control in the liver 6 months after the procedure had longer overall survival as well as patients with a liver progression-free interval post-procedure equal to or greater than 9 months. Patients with good performance status and normal liver function at baseline also had longer survival. The most common adverse reactions were nausea, fatigue, abdominal pain, and mild reversible abnormalities in liver function tests. Overall, our results suggest that radioembolization might be a safe and effective treatment option for patients with unresectable liver sarcomas.Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9–26.1 months), while median LPFS was 9 months (95% CI: 6.2–11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0–1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.

Liver-directed treatments of liver-dominant metastatic leiomyosarcoma

The purpose of this study was to determine the safety and efficacy of liver-directed therapies in patients with unresectable metastatic leiomyosarcoma to the liver. Liver-directed therapies included in this study were transarterial chemoembolization with doxorubicin eluting beads (DEB-TACE), yttrium-90 (Y90) radioembolization, and percutaneous microwave ablation. This is a single institution retrospective study of unresectable metastatic leiomyosarcoma to the liver treated with DEB-TACE, radioembolization, or microwave ablation. DEB-TACE was performed using 70-150 or 100-300 µ doxorubicin-loaded drug-eluting LC beads. Radioembolization was performed using Y90 glass microspheres. Electronic medical records were retrospectively reviewed to evaluate clinical and biochemical toxicities, tumor response on imaging, overall survival (OS), and liver progression-free survival (PFS). A total of 24 patients with metastatic leiomyosarcoma to the liver who underwent liver-directed treatment were identified (8 males, 16 females; average age, 62.8±11.4 years). Of these patients, 13 underwent DEB-TACE, 6 underwent Y90, and 5 underwent ablation. Three patients received a combination of treatments: one received Y90 followed by DEB-TACE, one received ablation followed by DEB-TACE, and one received ablation followed by Y90. Of the 24 patients, 19 received prior chemotherapy. At 3-month follow-up, grade 1 or 2 lab toxicities were found in 20 patients; 3 patients had grade 3 toxicities. A grade 3 clinical toxicity was reported in one patient. MELD score was 7.5±1.89 at baseline and 8.8±4.2 at 3 months. Median OS was 59 months (95% CI, 39.8-78.2) from diagnosis, 27 months (95% CI, 22.9-31.0) from development of liver metastasis, and 9 months (95% CI, 0-21.4) from first liver-directed treatment. Median liver PFS was 9 months (95% CI, 1.4-16.6). Treatment with liver-directed therapies for patients with unresectable metastatic leiomyosarcoma to the liver is safe and can improve overall survival, with OS after liver-directed therapy being similar to patients who underwent surgical resection.

Resection vs. ablation for lesions characterized as resectable-ablative within the colorectal liver oligometastases criteria: a propensity score matching from retrospective study.

BackgroundThere has been no prospective or retrospective studies reporting the comparison outcome between surgery and ablation for resectable-ablative (lesions could be treated by resection or complete ablation) colorectal liver oligometastases (CLOM). The purpose of this study was to compare the efficacy and prognostic difference in patients who underwent R0 resection vs. complete ablation within the resectable-ablative CLOM criteria.MethodsFrom January 2008 to May 2018, a total of 2,367 patients diagnosed with colorectal liver metastases were included in this observational study. The metastasis was characterized by only limited to liver with number ≤5, size ≤5 cm, and resectable-ablative (lesions could be treated by resection or complete ablation). The evaluated indications, including liver progression-free survival (LPFS), overall survival (OS), survival rates, pattern and number of recurrences, and complications, were compared by using propensity score matching (PSM). The Kaplan−Meier curves were generated, and a log-rank test was performed. The Cox regression model was used for univariate and multivariate analyses to identify predictors of outcomes.ResultsA total of 421 consecutive patients were eligible for this study, with 250 and 171 undergoing R0 resection and complete ablation, respectively. PSM identified 145 patients from each group. The 1-, 3-, 5- and 8-year OS rates in the resection group and the ablation group were 95.8% vs. 95.0%, 69.8% vs. 60.1%, 53.6% vs. 42.5%, and 45.1% vs. 32.9% (p = 0.075), respectively. The median LPFS in the resection group was significantly longer than that in the ablation group (35 months vs. 15 months, p = 0.011). No statistical difference was found in LPFS between the two groups when comparing ≤3 cm liver metastases. For liver metastasis >3 cm, the median LPFS in the resection group and ablation group was 11 months and 5 months, respectively (p = 0.001). In terms of high risk of clinical risk score (CRS), the resection group showed longer LPFS than the ablation group (median 18 months vs. 10 months, p = 0.043).ConclusionFor patients within the CLOM criteria suggesting that liver metastases were resectable as well as ablative, resection could result in longer liver recurrence-free survival than ablation in cases with size >3 cm or high risk of CRS. But for ≤3 cm liver metastases, their treatment efficacies were comparable.

Factors Affecting Oncologic Outcomes of 90Y Radioembolization of Heavily Pre-Treated Patients With Colon Cancer Liver Metastases

IntroductionThe purpose of this study was to identify predictors of overall (OS) and liver progression-free survival (LPFS) following Yttrium-90 radioembolization (RAE) of heavily pretreated patients with colorectal cancer liver metastases (CLM), as well as to create and validate a predictive nomogram for OS. Materials and MethodsMetabolic, anatomic, laboratory, pathologic, genetic, primary disease, and procedure-related factors, as well as pre- and post-RAE therapies in 103 patients with CLM treated with RAE from September 15, 2009 to March 21, 2017 were analyzed. LPFS was defined by Response Evaluation Criteria In Solid Tumors 1.1 and European Organization for Research and Treatment of Cancer criteria. Prognosticators of OS and LPFS were selected using univariate Cox regression, adjusted for clustering and competing risk analysis (for LPFS), and subsequently tested in multivariate analysis (MVA). The nomogram was built using R statistical software and internally validated using bootstrap resampling. ResultsPatients received RAE at a median of 30.9 months (range, 3.4-161.7 months) after detection of CLM. The median OS and LPFS were 11.3 months (95% confidence interval, 7.9-15.1 months) and 4 months (95% confidence interval, 3.3-4.8 months), respectively. Of the 40 parameters tested, 6 were independently associated with OS in MVA. These baseline parameters included number of extrahepatic disease sites (P < .001), carcinoembryonic antigen (P < .001), albumin (P = .005), alanine aminotransferase level (P < .001), tumor differentiation level (P < .001), and the sum of the 2 largest tumor diameters (P < .001). The 1-year OS of patients with total points of < 25 versus > 80 was 90% and 10%, respectively. Bootstrap resampling showed good discrimination (optimism corrected c-index = 0.745) and calibration (mean absolute prediction error = 0.299) of the nomogram. Only baseline maximum standardized uptake value was significant in MVA for LPFS prediction (P < .001; SHR = 1.06). ConclusionThe developed nomogram included 6 pre-RAE parameters and provided good prediction of survival post-RAE in heavily pretreated patients. Baseline maximum standardized uptake value was the single significant predictor of LPFS.

Prognostic value of carcinoembryonic antigen level in patients with colorectal cancer liver metastasis treated with percutaneous microwave ablation under ultrasound guidance

Thermal ablation is an alternative treatment for colorectal cancer liver metastasis (CRLM). However, prognostic factors in patients with CRLM who have undergone microwave ablation (MWA) have not been clearly defined. Therefore, this study aimed to analyze the risk factors associated with early recurrence in patients with CRLM treated with MWA.Herein, we retrospectively analyzed data for 140 patients with CRLM who underwent MWA from 2013 to 2015 in our institution. Patients were grouped by median pretreatment carcinoembryonic antigen (CEA) level into the high CEA level (>3.7 ng/mL) group and low CEA level (≤3.7 ng/mL) group. Variables that might affect overall survival were subjected to univariable and multivariable Cox regression analysis.Our results showed a median progression-free survival (PFS) and median liver progression-free survival (LPFS) of 9 and 11.5 months, respectively, for the 99 CRLM patients analyzed. Both the median PFS duration (7.5 vs. 12.0 months; hazard ratio [HR]: 1.852; 95% confidence interval [CI]: 1.131–3.034; P = .014) and LPFS duration (7.5 vs 14.0 months; HR: 2.117; 95% CI: 1.247–3.593; P = .005) were significantly shorter in the high CEA level group than in the low level group. In multivariable analysis, high CEA level, >3 tumors, and positive node status for the primary tumor were independent factors for PFS, with corrected HRs of 2.11 (95% CI: 1.257–3.555; P = .005), 2.450 (95% CI: 1.420–4.226; P = .001), and 2.265 (95% CI: 1.304–3.935; P = .004), respectively. However, age, tumor size, regional lymph node were not associated with LPFS.CEA level could be a valuable prognostic factor for early recurrence in patients with CRLM after MWA irrespective of the presence of early local recurrence in the liver or disease progression.

Outcomes of Radioembolization in Patients with Chemorefractory Colorectal Cancer Liver Metastasis: a Single-Center Experience.

We aimed to evaluate the efficacy and outcomes of radioembolization with Yttrium-90 (Y-90) microspheres in patients with unresectable and chemorefractory colorectal cancer liver metastasis (CRCLM). This single-center study included 43 patients (34 male, 9 female) who underwent radioembolization with Y-90 for unresectable, chemorefractory CRCLM between September 2008 and July 2014. Overall survival (OS), liver progression-free survival (LPFS), overall response rate (ORR), local disease control rate (LDCR), and relations of these parameters with patient disease characteristics were evaluated. OS and LPFS rates were compared according to microspheres. Survival rates were calculated with Kaplan-Meier method, and potential prognostic variables were evaluated on univariate analyses. Post-procedural median OS was 12.8months. LPFS was 5.6months. ORR was 33%, LDCR was 67% on 3rd month follow-up. Low tumor burden (< 25%) was associated with higher median OS after radioembolization (< 25 vs > 25-50% p < 0.0001 and < 25 vs > 50% p = 0.005). Patients with left colon tumors exhibited significantly longer median OS after metastasis than right colon tumors (p = 0.046). Extrahepatic disease and synchronicity showed poorer survival parameters; however, the difference was not significant (p = 0.1 and p = 0.3, respectively). In subgroup analyses, the distribution of patient number and characteristics showed heterogeneity as number of patients with low tumor burden was higher in resin Y-90 group. Resin Y-90 group exhibited significantly higher median OS and LPFS compared to glass Y-90 group (16.5 vs. 7months, p = 0.001; 6.73 vs. 3.38months, p = 0.023, respectively). Radioembolization is a safe local-regional treatment option in chemorefractory, inoperable CRCLM. Radioembolization at earlier stages may lead to more favorable results especially with lower tumor burden patients.

Expanded criteria for debulking of liver metastasis also apply to pancreatic neuroendocrine tumors

Recently, there has been a move toward decreasing the threshold for liver debulking for metastatic carcinoid tumors from 90% to 70%. The debulking threshold and factors that predict outcomes of liver debulking operations specifically among pancreatic neuroendocrine tumors are not well defined. Records of patients with pancreatic neuroendocrine tumors undergoing liver debulking with a threshold of 70% from 2006 to 2016 were reviewed. Extrahepatic metastases and positive margins by enucleation were allowed. Liver progression-free survival and overall survival were calculated by the Kaplan-Meier method for various factors and compared by log-rank. Factors also were correlated with liver progression-free survival and overall survival by multivariate regression analyses. Forty-two patients underwent 44 operations, of which 24 resulted in 100% debulking, 12 resulted in ≥90% debulking, and 8 resulted in ≥70% debulking. Median liver progression-free survival was 11 months. The 5-year overall survival rate was 81%. There were no significant differences in outcome based on percent debulked. Only liver metastasis ≥5 cm correlated with liver progression-free survival and overall survival. Consideration should be given to expanding the criteria for liver debulking in pancreatic neuroendocrine tumors to include a new threshold of >70% debulking, intermediate grade tumors, positive margins, and extrahepatic metastases; these criteria yield results indistinguishable from complete resection. Using these expanded criteria will increase the number of patients eligible for an operation and maintain high survival rates.

Surrogate Imaging Biomarkers of Response of Colorectal Liver Metastases After Salvage Radioembolization Using 90Y-Loaded Resin Microspheres.

The purpose of the present study is to evaluate Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, tumor attenuation criteria, Choi criteria, and European Organization for Research and Treatment of Cancer (EORTC) PET criteria as measures of response and subsequent predictors of liver progression-free survival (PFS) after radioembolization (RE) of colorectal liver metastases (CLM). The study also assesses interobserver variability for measuring tumor attenuation using a single 2D ROI on a simple PACS workstation. We performed a retrospective review of the clinical RE database at our institution, to identify patients treated in the salvage setting for CLM between December 2009 and March 2013. Response was evaluated on FDG PET scans, with the use of EORTC PET criteria, and on portal venous phase CT scans, with the use of RECIST 1.1, tumor attenuation criteria, and Choi criteria. Two independent blinded observers measured tumor attenuation using a single 2D ROI. The intraclass correlation coefficient (ICC) for interobserver variability was assessed. Kaplan-Meier methodology was used to calculate liver PFS, and the log-rank test was used to assess the response criteria as predictors of liver PFS. A total of 25 patients with 46 target tumors were enrolled in the study. The ICC was 0.95 at baseline and 0.98 at response evaluation. Among the 25 patients, more responders (i.e., partial response) were identified on the basis of EORTC PET criteria (n = 14), Choi criteria (n = 15), and tumor attenuation criteria (n = 13) than on the basis of RECIST 1.1 (n = 2). The median liver PFS was 3.0 months (95% CI, 2.1-4.0 months). Response identified on the basis of EORTC PET criteria (p < 0.001), Choi criteria (p < 0.001), or tumor attenuation criteria (p = 0.01) predicted liver PFS; however, response identified by RECIST 1.1 did not (p = 0.1). RECIST 1.1 has poor sensitivity for detecting metabolic responses classified by EORTC PET criteria. EORTC PET criteria, Choi criteria, and tumor attenuation criteria appear to be equally reliable surrogate imaging biomarkers of liver PFS after RE in patients with CLM.

Outcomes and Predictors of Toxicity after Selective Internal Radiation Therapy Using Yttrium-90 Resin Microspheres for Unresectable Hepatocellular Carcinoma.

We sought to report outcomes and toxicity in patients with hepatocellular carcinoma (HCC) who received resin yttrium-90 selective internal radiation therapy ((90)Y-SIRT) and to identify factors associated with declining liver function. Patients treated with (90)Y-SIRT were retrospectively evaluated. Radiographic response was assessed using RECIST 1.1. Median liver progression-free survival (LPFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Bivariate analysis was used to examine associations between change in Child-Pugh (CP) score/class and patient characteristics and treatment parameters. Twenty-seven patients with unresectable HCC underwent SIRT, 52% were CP Class A, 48% were Class B, 11% were BCLC stage B, and 89% were stage C. Forty-four percent of patients had portal vein thrombus at baseline. One-third of patients received bilobar treatment. Median activity was 32.1 mCi (range 9.18-43.25) and median--absorbed dose to the liver was 39.6 Gy (range 13.54-67.70). Median LPFS and OS were 2.5 and 11.7 months, respectively. Three-month disease control rate was 63 and 52% in the target lesions and whole liver, respectively. New onset or worsened from baseline clinical toxicities were confined to Grade 1-2 events. However, new or worsened Grade 3-4 laboratory toxicities occurred in 38% of patients at 3 months and 43% of patients at 6 months following SIRT (six had lymphocytopenia, three had hypoalbuminemia, and two had transaminasemia). After 3 months, six patients had worsened in CP score and five had worsened in class from baseline. After 6 months, four patients had worsened in CP score and one had worsened in class from baseline. Pretreatment bilirubinemia was associated with a 2+ increase in CP score within 3 months (P = 0.001) and 6 months (P = 0.039) of (90)Y-SIRT. Pretreatment transaminasemia and bilirubinemia were associated with increased CP class within 3 months of SIRT (P = 0.021 and 0.009, respectively). (90)Y-SIRT was well-tolerated in patients with unresectable HCC, with no Grade 3-4 clinical toxicities. However, Grade 3-4 laboratory toxicities and worsened CP scores were more frequent. HCC patients with pretreatment bilirubinemia or transaminasemia may be at higher risk of experiencing a decline in liver function following (90)Y-SIRT.

Radioembolization as a Salvage Therapy for Heavily Pretreated Patients With Colorectal Cancer Liver Metastases: Factors That Affect Outcomes

BackgroundIn this study we assessed the efficacy and factors that affect outcomes of radioembolization (RE) using yttrium-90 resin microspheres in patients with unresectable and chemorefractory colorectal cancer liver metastases (CLM). Patients and MethodsAfter an institutional review board waiver of approval, a review of a Health Insurance Portability and Accountability Act-registered, prospectively created and maintained database was performed. Data on patient demographic and disease characteristics, RE treatment parameters, and additional treatments were evaluated for significance in predicting overall survival (OS) and liver progression-free survival (LPFS). Complications were evaluated according to the National Cancer Institute Common Terminology Criteria for adverse events. ResultsFrom September 2009 to September 2013, 53 patients underwent RE at a median of 35 months after CLM diagnosis. Median OS was 12.7 months. Multivariate analysis showed that carcinoembryonic antigen levels at the time of RE ≥ 90 ng/mL (P = .004) and microscopic lymphovascular invasion of the primary (P = .002) were independent predictors of decreased OS. Median LPFS was 4.7 months. At 4 to 8 and 12 to 16 weeks after RE, most patients (80% and 61%, respectively) according to Response Evaluation Criteria in Solid Tumors (RECIST) had stable disease; additional evaluation using PET Response Criteria in Solid Tumors (PERCIST) led to reclassification in 77% of these cases (response or progression). No deaths were noted within the first 30 days. Within the first 90 days after RE, 4 patients (8%) developed liver failure and 5 patients (9%) died, all with evidence of disease progression. ConclusionRE in the salvage setting was well-tolerated, and permitted the administration of additional therapies and led to a median OS of 12.7 months. Evaluation using PERCIST was more likely than RECIST to document response or progression compared with the baseline assessment before RE.

Phase I Trial of Selective Internal Radiation Therapy for Chemorefractory Colorectal Cancer Liver Metastases Progressing After Hepatic Arterial Pump and Systemic Chemotherapy

IntroductionThis prospective study assessed the safety and outcomes of selective internal radiation therapy (SIRT) using yttrium-90 (90Y) resin microspheres as a salvage therapy for liver-predominant metastases of colorectal cancer in patients with documented progression after hepatic arterial chemotherapy (HAC) and systemic chemotherapy. Patients and MethodsWe recruited 19 patients who had received a mean of 2.9 prior lines of chemotherapy and ≥ 1 line of HAC. Dose-limiting toxicities (grade 3 or higher) were catalogued using Common Terminology Criteria for Adverse Events version 3.0. At 4 to 8 weeks and 3 to 4 months post SIRT, responses were assessed by carcinoembryonic antigen (CEA), and quantitative imaging using Response Evaluation Criteria in Solid Tumors (RECIST) and PET Response Criteria in Solid Tumors (PERCIST). Liver progression-free survival (LPFS), progression-free survival (PFS), and overall survival (OS) were calculated using Kaplan-Meier methodology. ResultsMedian follow-up was 31.2 months after SIRT. Within 6 weeks of SIRT, 3 patients (15.8%) experienced grade 3 toxicity. There was no incidence of radiation-induced liver disease. Responses by RECIST, PERCIST, and CEA were, respectively, 0%, 20%, and 32% at 4 to 8 weeks and 5%, 33%, and 21% at 3 to 4 months post SIRT; 53% of patients had stable disease (by RECIST) at 3 to 4 months. Of 19 patients, 4 (21.1%) had liver ablation, 9 (47%) received additional HAC, and 17 (89%) received systemic chemotherapy after SIRT. Median LPFS, PFS, and OS after SIRT were 5.2 months, 2.0 months, and 14.9 months, respectively. ConclusionSIRT was well tolerated and did not prohibit subsequent treatment, resulting in a median OS of 14.9 months in this heavily pretreated population.

Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases.

To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver metastases after the failure of tyrosine kinase inhibitors (TKIs). Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study. The patients were divided into two groups: those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care, those in control group only received TKI reintroduction or best supportive care. The primary end-point was overall survival and the secondary end-points were, progression-free survival (PFS), response rates, and safety. Sixty patients admitted between June 2008 and October 2011 were eligible for this study, including 22 in TACE group and 38 in control group. In the TACE group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease, and 5 (22.7%) had liver progressive disease. Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group. The median liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk, 95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI: 23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE had significantly better prognosis. Most of the adverse events were of grade 1 or 2 and tolerable. TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure, and it may be an optional treatment for this disease.