Yttrium-90 Radioembolization and Concomitant Systemic Gemcitabine,Cisplatin, and Capecitabine as the First-Line Therapy for Locally Advanced Intrahepatic Cholangiocarcinoma

PurposeTo determine the safety and effectiveness of yttrium-90 transarterial radioembolization (TARE) combined with systemic gemcitabine, cisplatin, and capecitabine for the first-line treatment of locally advanced intrahepatic cholangiocarcinoma (iCCA).Materials and MethodsData of 13 patients with treatment-naïve, locally advanced iCCA treated with a downstaging protocol using gemcitabine, cisplatin, TARE, and capecitabine were retrospectively reviewed. Overall survival (OS), local tumor response (modified Response Evaluation Criteria in Solid Tumors), progression-free survival (PFS), technical adverse events, and toxicity were measured.ResultsCalculated from the time of diagnosis, the median OS was 29 months (95% confidence interval [CI], 15 to not reached), with a 1-year OS of 84.6% (95% CI, 52.2%–95.9%) and 2-year OS of 52.9% (95% CI, 20.3%–77.5%). The median OS values were 24 months (95% CI, 8 to not reached) and 21 months (95% CI, 5 to not reached) from the time of initial cycle of chemotherapy and TARE, respectively. Patients who were downstaged to surgery (n = 7, 53.8%) had a more favorable OS (median OS, not reached vs 15 months; P = .0221). Complete and partial radiologic responses were achieved in 5 (38.5%) and 6 (46.2%) patients, respectively. The median PFS was 13 months (95% CI, 12 to not reached). Although no serum toxicity with Grade >2 occurred within 3 months after TARE, 1 patient was no longer a surgical candidate given suboptimal nutrition status despite successful downstage on imaging studies. Two patients required a reduced dose or delay of post-TARE chemotherapy.ConclusionsFirst-line combination therapy with TARE and systemic gemcitabine, cisplatin, and capecitabine is an effective treatment with an acceptable safety profile for iCCA with a high rate of downstaging to resection.     

Transarterial Radioembolization for Hepatocellular Carcinoma with Major Vascular Invasion: A Nationwide Propensity Score–Matched Analysis with Target Trial Emulation

PurposeTo examine National Cancer Database (NCDB) data to comparatively evaluate overall survival (OS) between patients undergoing transarterial radioembolization (TARE) and those undergoing systemic therapy for hepatocellular carcinoma with major vascular invasion (HCC-MVI).MethodsOne thousand five hundred fourteen patients with HCC-MVI undergoing first-line TARE or systemic therapy were identified from the NCDB. OS was compared using propensity score–matched Cox regression and landmark analysis. Efficacy was also compared within a target trial framework.ResultsTARE usage doubled between 2010 and 2015. Intervals before treatment were longer for TARE than for systemic therapy (mean [median], 66.5 [60] days vs 46.8 (35) days, respectively, P < .0001). In propensity-score–matched and landmark-time–adjusted analyses, TARE was found to be associated with a hazard ratio of 0.74 (95 % CI, 0.60–0.91; P = .005) and median OS of 7.1 months (95 % CI, 5.0–10.5) versus 4.9 months (95 % CI, 3.9–6.5) for systemically treated patients. In an emulated target trial involving 236 patients with unilobular HCC-MVI, a low number of comorbidities, creatinine levels <2.0 mg/dL, bilirubin levels <2.0 mg/dL, and international normalized ratio <1.7, TARE was found to be associated with a hazard ratio of 0.57 (95 % CI, 0.39–0.83; P = .004) and a median OS of 12.9 months (95 % CI, 7.6–19.2) versus 6.5 months (95 % CI, 3.6–11.1) for the systemic therapy arm.ConclusionsIn propensity-score–matched analyses involving pragmatic and target trial HCC-MVI cohorts, TARE was found to be associated with significant survival benefits compared with systemic therapy. Although not a substitute for prospective trials, these findings suggest that the increasing use of TARE for HCC-MVI is accompanied by improved OS. Further trials of TARE in patients with HCC-MVI are needed, especially to compare with newer systemic therapies.     

Socioeconomic and Survival Analysis of Radioembolization in Patients with Intrahepatic Cholangiocarcinoma: A Propensity Score–Adjusted Study

PurposeTo determine whether transarterial radioembolization (TARE) is associated with longer survival of patients with intrahepatic cholangiocarcinoma (ICC) and whether access to TARE is influenced by socioeconomic factors.Materials and MethodsRetrospective review of patients with ICC in the National Cancer Database from 2004 to 2018 was performed with Cox regression analysis to identify predictors of survival. Overall survival (OS) was estimated using the Kaplan-Meier method. Socioeconomic factors were compared between 2 groups using the Wilcoxon rank-sum test and χ² test. Propensity score–matched cohorts were created between patients with ICC who did and did not undergo TARE.ResultsThe number of patients receiving TARE for ICC increased over time from 1 in 2004 to 210 in 2018. Patients in the TARE group were more likely to be White (87.9% vs 84.3%; P = .012) and less likely to be Hispanic/Latino (7.7% vs 11.0%; P = .009). Fewer patients who underwent TARE were uninsured (0.9% vs 2.8%; P = .012). Older age, male sex, non-White race, higher tumor grade size, and stage, earlier year of diagnosis, lack of treatment with surgery or systemic therapy, and presence of lymphatic or vascular invasion exhibited significant associations with decreased survival (P < .05 for all). Patients who underwent TARE had longer survival in both unadjusted and adjusted cohorts, with an OS of 17.5 months (vs 7.2 months in the non-TARE group) after propensity matching.ConclusionsPatients with ICC who had undergone TARE experienced significantly longer survival than that experienced by those who had not after adjusting for measurable confounders. Significant socioeconomic disparities in access to TARE remain.     

Chronic Hepatotoxicity in Patients with Metastatic Neuroendocrine Tumor: Transarterial Chemoembolization versus Transarterial Radioembolization

PurposeTo compare the manifestations of chronic liver injury following transarterial chemoembolization with those of transarterial radioembolization (TARE) in patients with neuroendocrine tumor (NET).Materials and MethodsThis study consisted of an Institutional Review Board-approved single-institution retrospective analysis of NET patients who received transarterial chemoembolization from 2006 to 2016 and TARE from 2005 to 2014 and survived at least 1 year from the initial treatment. Patients receiving only transarterial chemoembolization (n = 63) or TARE (n = 28) were evaluated for the presence or absence of durable hepatic toxicities occurring at least 6 months after initial treatment. The definitions and grades of liver injury were adapted from Common Terminology Criteria for Adverse Events version 4.0 and were characterized by the presence of laboratory or clinical toxicities of Grade 3 or above.ResultsChronic hepatic toxicity occurred in 14 of 63 transarterial chemoembolization patients (22%) with a total of 26 Grade 3-4 events, in whom elevation of bilirubin was the most common toxicity, compared to 8 of 28 TARE patients (29%) with a total of 16 Grade 3-4 and 2 Grade 5 events, in whom ascites were the most frequent toxicity. There were more laboratory toxicities in the transarterial chemoembolization group (65% vs 38%, P = .11) and fewer Grade 4–5 injuries (6% vs 27% of patients, P = .06). There was also a significantly higher number of patients who experienced intrahepatic progression of disease in the transarterial chemoembolization cohort than in the TARE patients (75% vs 43%, respectively; P = .005).ConclusionsDelayed hepatotoxicity from transarterial chemoembolization and TARE occurred in 22% and 29% of patients, respectively, from 6 months to several years following treatment. Transarterial chemoembolization-related toxicities on average were less severe and manifested primarily as laboratory derangements, compared to TARE toxicities which consisted of clinical hepatic decompensation.     

Induction of Contralateral Hepatic Hypertrophy by Unilobar Yttrium-90 Transarterial Radioembolization versus Portal Vein Embolization: An Animal Study

PurposeTo compare hepatic hypertrophy in the contralateral lobe achieved by unilobar transarterial radioembolization (TARE) versus portal vein embolization (PVE) in a swine model.MethodsAfter an escalation study to determine the optimum dose to achieve hypertrophy after unilobar TARE in 4 animals, 16 pigs were treated by TARE (yttrium-90 resin microspheres) or PVE (lipiodol/n-butyl cyanoacrylate). Liver volume was calculated based on CT before treatment and during 6 months of follow-up. Independent t-test (P < .05) was used to compare hypertrophy. The relationship between hypertrophy after TARE and absorbed dose was calculated using the Pearson correlation.ResultsAt 2 and 4 weeks after treatment, a significantly higher degree of future liver remnant hypertrophy was observed in the PVE group versus the TARE group, with a median volume gain of 31% (interquartile range [IQR]: 16%–66%) for PVE versus 23% (IQR: 6%–36%) for TARE after 2 weeks and 51% (IQR: 47%–69%) for PVE versus 29% (IQR: 20%–50%) for TARE after 4 weeks. After 3 and 6 months, hypertrophy converged without a statistically significant difference, with a volume gain of 103% (IQR: 86%–119%) for PVE versus 82% (IQR: 70%–96%) for TARE after 3 months and 115% (IQR: 70%–46%) for PVE versus 86% (IQR: 58%–111%) for TARE after 6 months. A strong correlation was observed between radiation dose (median 162 Gy, IQR: 139–175) and hypertrophy.ConclusionsPVE resulted in rapid hypertrophy within 1 month of the procedure, followed by a plateau, whereas TARE resulted in comparable hypertrophy by 3–6 months. TARE-induced hypertrophy correlated with radiation absorbed dose.     

Multicenter Evaluation of Survival and Toxicities of Hepatocellular Carcinoma following Radioembolization: Analysis of the RESiN Registry

PurposeTo determine overall survival (OS), progression-free survival (PFS), and toxicity in patients with hepatocellular carcinoma (HCC) in a multicenter, real-world data registry using transarterial radioembolization (TARE) with resin microspheres.Materials and MethodsA total of 448 patients with HCC were treated at 36 centers between 2015 and 2019. Treatment history, baseline laboratory and imaging, and treatment goal were assessed. OS and PFS were stratified using Barcelona Clinic Liver Cancer (BCLC) and Child-Pugh (CP) classifications. Kaplan-Meier analyses compared OS and PFS with 95% confidence intervals. Transplants were tracked. Toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox proportional hazard of baseline demographics assessed factors affecting survival.ResultsPrior chemoembolization and systemic therapy were used in 107 (26%) and 68 (16%) patients, respectively. Using the BCLC staging system, 66 patients (19%) were BCLC A and 202, 51, and 26 were BCLC B, C, and D, respectively. Median OS for patients with BCLC A disease was not achieved at 30 months. Median OS for patients with BCLC B, C, and D disease were 19.5, 13.6, and 11.5 months, respectively (P = .0006). Median PFS for patients with BCLC A, B, C, and D were 19.8, 10.0, 6.3, and 5.9 months, respectively (P = .003). Twenty patients underwent transplantation, representing 14 of 43 (33%) and 6 of 28 (21%) patients who underwent bridging and downstaging therapy, respectively. Common Grade 3 toxicities were encephalopathy (11/448, 2.5%), hyperbilirubinemia (10/448, 2.2%), and ascites (9/448, 2.0%). Factors predicting longer survival included CP A (χ² = 4.2, P = .04) and BCLC A (χ² = 5.2, P = .02).ConclusionsIn a frequently pretreated patient cohort with disease burden in 81% beyond the Milan criteria, TARE with resin microspheres provided OS comparable to other studies in this multicenter registry.     

Transarterial Radioembolization Treatment of Pancreatic Cancer Patients with Liver-Dominant Metastatic Disease Using Yttrium-90 Glass Microspheres: A Single-Institution Retrospective Study

PurposeTo retrospectively evaluate the safety and efficacy of transarterial radioembolization (TARE) with yttrium-90 (⁹⁰Y)-labeled glass microspheres in pancreatic adenocarcinoma patients with liver-dominant metastatic disease.Materials and MethodsThis retrospective, single-center study evaluated 26 patients (12 men and 14 women; mean age, 65.5 ± 11.2 years) with liver-dominant metastatic pancreatic cancer who were treated with TARE from April 2010 to September 2017. All patients received systemic chemotherapy before TARE, and 19 received systemic therapy after embolization. Nineteen patients had extrahepatic disease at the time of TARE. Response to treatment was determined by Response Evaluation Criteria in Solid Tumors at 3 months.ResultsMedian overall survival (OS) from pancreatic cancer diagnosis was 33.0 months (range, 8.5–87.5 months); median OS from diagnosis of liver metastasis was 21.8 months (range, 2.0–86.2 months); and median OS from TARE treatment was 7.0 months (range, 1.0–84.1 months). Grade 1–2 clinical toxicities were noted in 21 patients (80.8%), and 24 patients (92.3%) had grade 1–2 biochemical toxicities. Four patients (15.4%) had grade 3 clinical toxicities, and 6 patients (23.1%) had grade 3 biochemical toxicities. Imaging was available in 22 patients (84.6%) and demonstrated partial response in 1 patient, stable disease in 9 patients, and progressive disease in 12 patients. Improved hepatic progression-free survival was associated in patients younger than 65 years and in those whose carbohydrate antigen 19-9 level decreased or remained stable after treatment.ConclusionsTARE with ⁹⁰Y-labeled glass microspheres is safe and led to promising OS in liver-dominant metastatic pancreatic cancer.     

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.     

Alpha-Fetoprotein,Des-Gamma-Carboxy Prothrombin,and Modified RECIST Response as Predictors of Survival after Transarterial Radioembolization for Hepatocellular Carcinoma

PurposeTo evaluate the prognostic role of alpha-fetoprotein (AFP), des-gamma-carboxy protein (DCP), and modified Response Evaluation Criteria in Solid Tumors (mRECIST) in patients with hepatocellular carcinoma after transarterial radioembolization (TARE).Materials and MethodsDuring 2009–2016, 63 patients with AFP >20 ng/mL, DCP >20 mAU/mL, and Child-Pugh class A who were treated with TARE were evaluated using landmark and risk-of-death method after TARE. Both resin microspheres (n = 46) and glass microspheres (n = 17) were used. AFP or DCP response was defined as more than 50% decrease from baseline. mRECIST response was defined as complete or partial response. Median age was 60 years, and the proportion of male sex was 77.8% (n = 49). The proportions of patients with Barcelona Clinic Liver Cancer stages A, B, and C were 7.9% (n = 5), 46.0% (n = 29), and 46.0% (n = 29), respectively.ResultsAt the 3-month landmark, AFP, DCP, and mRECIST responders lived longer than nonresponders (median overall survival, 75.8 vs 7.6 months for AFP; 75.8 vs 7.1 months for DCP; and 75.8 vs 10.0 months for mRECIST; all P < .05). The 6-month risk of death at the 3-month landmark was statistically different only between DCP responders and nonresponders (P = .002). In multivariate analysis, age less than 70 years (P = .024), absence of distant metastasis (P = .049), DCP response (P = .003), and mRECIST response (P = .003) were independent predictors for overall survival at the 3-month landmark after TARE.ConclusionsAFP, DCP, and mRECIST responders showed better prognosis than nonresponders after TARE, and DCP response was a more potent predictor than AFP response. Tumor marker response, as well as radiologic response, may be useful to predict post-TARE survival.     

Transarterial Radioembolization for Hepatic Metastases of Pancreatic Adenocarcinoma: A Systematic Review

PurposeTo assess the safety and effectiveness of transarterial radioembolization (TARE) in the treatment of hepatic metastases from pancreatic ductal adenocarcinoma (PDAC).Materials and MethodsA systematic search of the Embase and MEDLINE databases was conducted using keywords and Medical Subject Headings terms related to TARE and hepatic metastases from PDAC. Observational studies and clinical trials reporting overall survival (OS), hepatic progression-free survival (hPFS), or tumor response after TARE were included.ResultsEight studies, comprising 145 patients with metastatic PDAC, met the inclusion criteria. No randomized controlled trials were identified, and 4 studies were prospective. Forty-four (30.3%) patients underwent previous pancreatic resection, and 66 (45.5%) had extrahepatic metastases at the time of TARE. Most studies (n = 6) used resin microspheres for TARE. The pooled disease control rate was 69.4% at a median of 3 months. The median OS from the time of TARE ranged from 3.7 to 9 months. The median hPFS ranged from 2.4 to 5.2 months. There were 31 Grade 3–4 biochemical toxicities and 4 treatment-related deaths.ConclusionsThe role of TARE in patients with hepatic metastases from PDAC remains unclear owing to low patient numbers, limited prospective data, and heterogeneity in the study design. Further prospective studies are required to evaluate the role of TARE in carefully selected patients with liver-only metastatic disease.     

Transarterial Radioembolization versus Transarterial Chemoembolization Plus Percutaneous Ablation for Unresectable,Solitary Hepatocellular Carcinoma of ≥3 cm: A Propensity Score–Matched Study

PurposeTo compare the safety and effectiveness of transarterial radioembolization (TARE) and transarterial chemoembolization with drug-eluting embolic agents combined with percutaneous ablation (transarterial chemoembolization [TACE] + ablation) in the treatment of treatment-naïve, unresectable, solitary hepatocellular carcinoma (HCC) of ≥3 cm.Materials and MethodsTwenty-nine patients with treatment-naïve, unresectable, solitary HCC of ≥3 cm received combined TACE + ablation, and 40 patients received TARE at a single institution. Local tumor response, tumor progression-free survival (PFS), overall survival, need for reintervention, bridge to transplant, and major complications were compared. Clinical variables and outcomes were compared before and after propensity score matching (PSM).ResultsBefore PSM, patients who underwent TARE had a larger tumor size (3.7 vs 5.5 cm; P = .0005) and were older (61.5 vs 69.3 years; P = .0014). After PSM, there was no difference in baseline characteristics between the 2 groups, with the mean tumor sizes measuring 3.9 and 4.1 cm in the TACE + ablation and TARE cohorts, respectively. After PSM (n = 19 in each group), no statistically significant difference was observed in local radiological response (disease control rates, 100% vs 94.7%; P = .31), survival (subdistribution hazard ratio [SHR], 0.71; 95% confidence interval [CI], 0.28–1.80; P = .469), PFS (SHR, 0.61; 95% CI, 0.21–1.71; P = .342), bridge to transplant (21.1% vs 31.6%, P = .46), and major adverse event rates (15.8% vs 10.5%, P = .63) between the 2 groups. The mean total number of locoregional interventions was higher in the TACE + ablation cohort (1.9 vs 1.3 sessions, P = .02), with an earlier median reintervention trend (SHR, 0.61; 95% CI, 0.20–1.32; P = .167).ConclusionsThe present study showed that TARE and the combination of TACE and ablation are comparable in safety and effectiveness for treating treatment-naïve, unresectable, solitary HCC of ≥3 cm.     

Neoadjuvant Yttrium-90 Transarterial Radioembolization with Resin Microspheres Prescribed Using the Medical Internal Radiation Dose Model for Intrahepatic Cholangiocarcinoma

PurposeTo evaluate outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) undergoing neoadjuvant yttrium-90 (⁹⁰Y) transarterial radioembolization (TARE) with resin microspheres prescribed using the Medical Internal Radiation Dose (MIRD) model.Materials and MethodsThis retrospective institutional review board–approved study included 37 patients with iCCA treated with ⁹⁰Y-TARE from October 2015 to September 2020. The primary outcome was overall survival (OS) from ⁹⁰Y-TARE. The secondary outcomes were progression-free survival (PFS), Response Evaluation Criteria In Solid Tumors 1.1 imaging response, and downstaging to resection. Patients with tumor proximity to the middle hepatic vein (<1 cm) and/or insufficient future liver remnant were treated with neoadjuvant intent (n = 21). Patients were censored at the time of surgery or at the last follow-up for the Kaplan-Meier survival analysis.ResultsFor 31 patients (69 years; interquartile range, 64–74 years; 20 men [65%]) included in the study, the first-line therapy was ⁹⁰Y-TARE for 23 (74%) patients. Imaging assessment at 6 months showed a disease control rate of 86%. The median PFS was 5.4 months (95% confidence interval [CI], 3–not reached). The PFS was higher after first-line ⁹⁰Y-TARE (7.4 months [95% CI, 5.3–not reached]) than that after subsequent ⁹⁰Y-TARE (2.7 months [95% CI, 2–not reached]) (P = .007). The median OS was 22 months (95% CI, 7.3–not reached). The 1- and 2-year OS rates were 60% (95% CI, 41%–86%) and 40% (95% CI, 19.5%–81%). In patients treated with neoadjuvant intent, 11 of 21 patients (52%) underwent resections. The resection margins were R0 and R1 in 8 (73%) and 3 (27%) of 11 patients, respectively. On histological review in 10 patients, necrosis of ≥90% tumor was achieved in 7 of 10 patients (70%).ConclusionsFirst-line ⁹⁰Y-TARE prescribed using the MIRD model as neoadjuvant therapy for iCCA results in good survival outcome and R0 resection for unresectable patients.     

Radioembolization for Intermediate-Stage Hepatocellular Carcinoma Maintains Liver Function and Permits Systemic Therapy at Progression

PurposeTo assess the liver function trends in patients with intermediate-stage (Barcelona Clinic Liver Cancer [BCLC] Stage B) hepatocellular carcinoma (HCC) who underwent yttrium-90 transarterial radioembolization (TARE) in response to a growing concern that liver-directed therapies negatively affect liver function and prevent patients with HCC from systemic therapy candidacy.Materials and MethodsAn HCC/TARE database (2004–2017) was retrospectively reviewed. Patients with BCLC Stage B/Child–Pugh (CP)-A HCC with laboratory test and imaging data at baseline and for at least 1 month after TARE were included. Follow-ups were at 3-month intervals. CP stage was assessed at each time point. End points included time to persistent CP-B status, time to CP-C status, and median overall survival (OS). Time–to–end point analyses were performed using the Kaplan–Meier method.ResultsSeventy-four patients (80% men, with a mean age of 63 years) with mostly (62%) bilobar disease underwent 186 TARE treatments (median, 2; range, 1–8). The median time to second TARE was 2.3 months (range, 1.7–6.4 months), and the median times to third and fourth TAREs were 11.7 months (range, 7.5–15 months) and 17.3 months (range, 11.5–23.1 months), respectively. Forty-three (58%) patients developed persistent CP-B HCC at a median time of 15.4 months (95% CI, 9.2–25.3 months); 17 (23%) patients developed CP-C HCC at a median time of 87.2 months (95% CI, 39.8–136.1 months). The median OS censored to transplantation was 30.4 months (95% CI, 22.7–37.4 months). On univariate and multivariate analyses, baseline albumin was a significant prognosticator of OS, whereas baseline albumin and bilirubin were significant prognosticators of time to persistent CP-B HCC and time to CP-C HCC.ConclusionsIn patients with CP-A HCC who underwent TARE for BCLC Stage B HCC, the median time to persistent CP-B HCC was 15.4 months. These findings indicate that patients would be candidates for systemic therapy at progression if indicated.     

Efficacy and Safety of Percutaneous Argon-Helium Cryoablation for Hepatocellular Carcinoma Abutting the Diaphragm

PurposeTo evaluate the efficacy and safety of percutaneous argon-helium cryoablation (CA) for hepatocellular carcinoma (HCC) abutting the diaphragm (<5 mm).Materials and MethodsA total of 61 consecutive patients (50 men, 11 women; mean age, 56.3 ± 12.1 years old; range, 32–83 years) with 74 HCC tumors (mean size, 3.3 ± 1.7 cm; range, 0.8–7 cm) who were treated with percutaneous argon-helium CA were enrolled in this retrospective study. Adverse events were evaluated according to Common Terminology Criteria for Adverse Events, version 5.0. Local tumor progression (LTP) and overall survival (OS) were analyzed using the Kaplan-Meier method and the log-rank test. The risk factors associated with OS and LTP were evaluated using univariate and multivariate Cox regression analysis.ResultsNo periprocedural (30-day) deaths occurred. A total of 29 intrathoracic adverse events occurred in 24 of the 61 patients. Major adverse events were reported in 5 patients (pleural effusion requiring catheter drainage in 4 patients and pneumothorax requiring catheter placement in 1 patient). Median follow-up was 18.7 months (range, 2.3–60.0 months). Median time to LTP after CA was 20.9 months (interquartile range [IQR], 14.1–30.6 months). Median times of OS after CA and diagnosis were 27.3 months (IQR, 15.1–45.1 months) and 40.9 months (interquartile range, 24.8–68.6 months), respectively. Independent prognostic factors for OS included tumor location (left lobe vs right lobe; hazard ratio [HR], 2.031; 95% confidence interval [CI], 1.062–3.885; P = .032) and number of intrahepatic tumors (solitary vs multifocal; HR, 2.684; 95% CI, 1.322–5.447; P = .006). Independent prognostic factors for LTP included age (HR, 0.931; 95% CI, 0.900–0.963; P < .001), guidance modality (ultrasound vs computed tomography and US; HR, 6.156 95% CI, 1.862–20.348; P = .003) and origin of liver disease.ConclusionsPercutaneous argon-helium CA is safe for the treatment of HCC abutting the diaphragm, with acceptable LTP and OS.     

Yttrium-90 Radioembolization in Intrahepatic Cholangiocarcinoma: A Multicenter Retrospective Analysis

PurposeTo report outcomes of yttrium-90 (⁹⁰Y) radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsRetrospective review was performed of 115 patients at 6 tertiary care centers; 92 were treated with resin microspheres (80%), 22 were treated with glass microspheres (19%), and 1 was treated with both. Postintervention outcomes were compared between groups with χ² tests. Survival after diagnosis and after treatment was assessed by Kaplan–Meier method.ResultsGrade 3 laboratory toxicity was observed in 4 patients (4%); no difference in toxicity profile between resin and glass microspheres was observed (P = .350). Clinical toxicity per Society of Interventional Radiology criteria was noted in 29 patients (25%). Partial response per Response Evaluation Criteria In Solid Tumors 1.1 was noted in 25% of patients who underwent embolization with glass microspheres and 3% of patients who were treated with resin microspheres (P = .008). Median overall survival (OS) from first diagnosis was 29 months (95% confidence interval [CI], 21–37 mo) for all patients, and 1-, 3-, and 5-year OS rates were 85%, 31%, and 8%, respectively. Median OS after treatment was 11 months (95% CI, 8–13 mo), and 1- and 3-year OS rates were 44% and 4%, respectively. These estimates were not significantly different between resin and glass microspheres (P = .730 and P = .475, respectively). Five patients were able to undergo curative-intent resection after ⁹⁰Y radioembolization (4%).ConclusionsThis study provides observational data of treatment outcomes after ⁹⁰Y radioembolization in patients with unresectable ICC.     

Transarterial Chemoembolization Followed by Radiofrequency Ablation for Hepatocellular Carcinoma: Impact of the Time Interval between the Two Treatments on Outcome

PurposeTo compare the efficacy of radiofrequency (RF) ablation after transarterial chemoembolization within or beyond 30 days for medium-large or multiple recurrent hepatocellular carcinomas (HCCs).Materials and MethodsIn this single-center retrospective study conducted from 2007 through 2015, 135 patients with a single recurrent HCC (>3 cm) or multiple (2–5 tumors) recurrent HCCs underwent transarterial chemoembolization plus RF ablation. A total of 62 patients underwent RF ablation after transarterial chemoembolization within 30 days (sequential group) and 73 patients underwent RF ablation after transarterial chemoembolization beyond 30 days (delayed group). Outcomes of interests included overall survival (OS), progression-free survival (PFS), and complete response (CR) rate.ResultsThe median OS and PFS were 49.8 and 38.0 months for sequential group, and 31.0 and 11.6 months for the delayed group. The sequential group experienced significantly better OS (hazard ratio [HR]: 0.517; P = .002) and PFS (HR, 0.621; P = .021). Among patients with multiple tumors or a single tumor >5 cm, the sequential group still had significantly longer OS (P = .022; P = .018, respectively) and PFS (P = 0.042; P = .036, respectively) than the delayed group, although no significant differences were observed among patients with solitary 3- to 5-cm tumors (P = .138; P = .803, respectively). The sequential group had a significantly better CR rate than the delayed group (85.4% vs. 68.5%, respectively; P = .035). Significant predictors of OS and PFS included maximum tumor size, number of tumors, and time interval between transarterial chemoembolization and RF ablation.ConclusionsTransarterial chemoembolization plus sequential RF ablation within 30 days was more effective for recurrent HCCs than transarterial chemoembolization plus delayed RF ablation. The time interval within 30 days is required for treating large or multiple HCCs but may not be necessary for solitary medium-sized HCC.     

Clinical Safety and Efficacy of Locoregional Therapy Combined with Adoptive Transfer of Allogeneic γδ T Cells for Advanced Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma

PurposeTo investigate the safety and efficacy of locoregional therapy plus adoptive transfer of allogeneic gamma delta (γδ) T cells for patients with hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC).MethodsThirty patients with HCC and 29 patients with ICC were randomly assigned to receive locoregional therapy (HCC, Group A, n = 15; ICC, Group C, n = 15) or locoregional therapy plus γδ T cell therapy (HCC, Group B, n = 15; ICC, Group D, n = 14). Groups A and C only received locoregional ablation (cryoablation or irreversible electroporation), whereas Groups B and D received locoregional therapy followed by adoptive transfer of allogeneic γδ T cells. The primary endpoints were safety, distant progression-free survival (PFS), local PFS, and overall survival (OS).ResultsThe median distant PFS was significantly longer in the combined treatment groups than the locoregional treatment groups (HCC: 8 vs 4 months, P = .04; ICC: 8 vs 4 months, P = .021). There was no significant difference in local PFS between the 2 treatment modalities. Patients with HCC in the combined treatment group had a longer OS (median OS: 13 vs 8 months, P = .029). However, there was no significant difference in OS in patients with ICC between the 2 treatment modalities (median OS: 9.5 vs 8 months, P = .546). All adverse events were manageable with no significant difference in incidence between groups.ConclusionsThe novel combination of locoregional ablation with adoptive transfer of allogeneic γδ cells was safe, with encouraging clinical efficacy against HCC and ICC.     

Direct-Acting Antivirals Improve Overall Survival in Interventional Oncology Patients with Hepatitis C and Hepatocellular Carcinoma

PurposeTo investigate the impact of direct-acting antivirals (DAAs) and 12-week sustained virologic response (SVR12) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) treated by interventional oncology (IO) therapies.Materials and MethodsRetrospective analysis of patients diagnosed from 2005 to 2016 with HCC and receiving IO therapies. A total of 478 patients met inclusion criteria. Patients were age 29–90 years (mean 63.6 ± 9.4 years) and 78.9% (n =3 77) male. Two hundred and eighty-five (57%) patients had chronic HCV, 93 (33%) received DAAs, and 63 (68%) achieved SVR12. Liver function, tumor characteristics, and IO therapy including ablation, image-guided transcatheter tumor therapies (ITTT) (eg, chemoembolization and radioembolization), and combination locoregional therapy were assessed in analysis.ResultsMedian overall survival (OS) of the cohort was 26.7 months (95% confidence interval [CI] 21.9–29.9). OS for ablation, combination locoregional therapy and ITTT, was 37.3 (CI 30.7–49.9), 29.3 (CI 24.2–38.0), and 19.7 months (CI 16.5–22.8), respectively (P < .0001). OS in patients with HCV was 30.7 months (CI 24.2–35.2) versus 22.2 months in non-HCV patients (CI 17.8–27.8, P = .03). Patients with HCV who received DAA had higher survival, 49.2 months (CI 36.5–not reached) versus those not receiving DAA, 18.5 months (CI 14.1–25.3, P < .0001). OS was 71.8 months (CI 42.3–not reached) for patients who achieved SVR12 after DAA versus 26.7 months in the non-SVR12 group (CI 15.9–31.1, P < .0001). Multivariable analysis revealed independent factors for OS including IO treatment type, DAA use and achieving SVR12 (P < .05).ConclusionsDAA use and SVR12 is associated with higher OS in patients with HCV-related HCC treated by IO therapies.     

Toxicity and Survival of Hepatocellular Carcinoma Patients with Hepatitis B Infection Treated with Yttrium-90 Radioembolization: An Updated 15-Year Study

PurposeTo evaluate the toxicity and survival of hepatocellular carcinoma (HCC) secondary to hepatitis B virus (HBV) infection treated with yttrium-90 transarterial radioembolization (TARE) over a 15-year period.Materials and MethodsThis study retrospectively analyzed 93 consecutive patients with HBV HCC—all derived from an original cohort of 1,000 patients—who were treated with TARE via standard radiation segmentectomy/lobectomy between December 2003 and December 2018. This group comprised 80 males and 13 females, with 79 having only HBV and 14 having additional liver comorbidities. Toxicity grades were determined by Common Terminology Criteria for Adverse Events, version 5.0. Overall survival (OS) was reported using intention-to-treat (ITT), censored, or competing risk. Univariate/multivariate analyses were used to evaluate predictors of OS.ResultsPosttreatment grade 3/4 toxicities included albumin (1.1%), bilirubin (4.3%), aspartate transaminase (6.5%), and alanine transaminase (3.2%). Median censored OS was 16.9 months (95% confidence interval [CI], 11.8–23.5): 17.5 months (95% CI, 11.5–86.9) for Child-Pugh (CP) A and 14.5 months (95% CI, 5.2–22.5) for CP B; not reached, 16.9 months (95% CI, 11.2–68.7), and 11.5 months (95% CI, 8.6–17.5) for Barcelona Clinic Liver Cancer (BCLC) A, B, and C, respectively. Multivariate analysis revealed albumin, alpha-fetoprotein, and portal vein thrombosis as independent predictors of ITT OS and albumin and tumor size as predictors when curative therapy was assigned as a competing risk.ConclusionsThis retrospective study showed that TARE therapy resulted in minimal toxicity in patients with HBV-derived HCC. Patients with CP A or BCLC A disease had superior survival outcomes compared to patients with CP B and BCLC B/C disease. These findings suggest that TARE is a viable treatment option for certain patient groups with HCC tumors secondary to HBV infection.     

Value of CT-Guided Percutaneous Irreversible Electroporation Added to FOLFIRINOX Chemotherapy in Locally Advanced Pancreatic Cancer: A Post Hoc Comparison

PurposeTo compare survival after CT-guided percutaneous irreversible electroporation (IRE) and folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) chemotherapy versus FOLFIRINOX only in patients with locally advanced pancreatic cancer (LAPC).Materials and MethodsA post hoc comparison was performed of data derived from a prospective IRE-FOLFIRINOX cohort and a retrospective FOLFIRINOX-only cohort. All patients received a minimum of 3 cycles of FOLFIRINOX for LAPC and were considered eligible for CT-guided percutaneous IRE. Endpoints included overall survival (OS), local and distant progression-free survival, and time to progression (TTP) and were compared using stratified Kaplan-Meier analysis. Patients who received > 8 cycles of FOLFIRINOX before IRE and who had tumors > 6 cm in the FOLFIRINOX-only group were excluded.ResultsOf 103 patients with a diagnosis of LAPC, 52 were deemed eligible (n = 30 IRE-FOLFIRINOX and n = 22 FOLFIRINOX-only). Patients in the FOLFIRINOX-only arm had larger tumors (53 mm ± 19 vs 38 mm ± 7, P = .340), had more locoregional lymph node metastases (23% vs 7%, P = .622), and more often received radiotherapy (7 patients vs 2 patients, P = .027); all other baseline characteristics were comparable. Median OS was 17.0 months (range, 5–35 mo; SD = 6) for IRE-FOLFIRINOX versus 12.4 months (range, 3–22 mo; SD = 6) for FOLFIRINOX-only (P = .038). After sensitivity analyses, median OS was 17.2 months (range, 6–27 mo; SD = 6) versus 12.4 months (range, 7–32 mo; SD = 10) (P = .05). Median TTP was longer in the IRE-FOLFIRINOX group: 14.2 months (range, 5–25 mo; SD = 4) versus 5.2 months (range, 2–22; SD = 6) (P = .0001).ConclusionsIn patients with LAPC after FOLFIRINOX chemotherapy, CT-guided percutaneous IRE may improve OS and TTP. This study may facilitate the design of randomized controlled trials to compare survival after IRE-FOLRINOX versus FOLFIRINOX-only.