Radiofrequency Ablation versus Transarterial Chemoembolization in Patients with Hepatocellular Carcinoma Awaiting Liver Transplant: An Analysis of the Scientific Registry of Transplant Recipients

PurposeTo evaluate differences in waitlist mortality and dropout in liver transplant candidates with hepatocellular carcinoma (HCC) who undergo radiofrequency (RF) ablation versus transarterial chemoembolization (TACE).Material and MethodsFrom 2004 to 2013, 11,824 patients with HCC in the Scientific Registry of Transplant Recipients who underwent RF ablation or TACE were included and followed until December 31, 2019, or 5 years, whichever came first, and were stratified by the Milan criteria. Competing risk and Cox regression analyses to compare waitlist mortality and dropout were performed using adjusted hazard ratios (asHRs, with RF ablation group as reference). Regression models were adjusted for age, race, sex, calculated Model for End-Stage Liver Disease score, tumor size, and number.ResultsThere was no difference in waitlist mortality and dropout for patients outside the Milan criteria (n = 1,226) who underwent TACE (19.2%) or RF ablation (19.0%) (asHR, 0.91; 95% CI, 0.79–1.03). There was also no difference for patients inside the Milan criteria (n = 10,598) in waitlist mortality/dropout (TACE 13.4% vs RF ablation 12.9%) (asHR, 1.29; 95% CI, 0.79–2.09). A subgroup analysis within the Milan criteria demonstrated no difference between TACE and RF ablation treatments in patients with a single tumor of ≤3 cm (asHR, 0.92; 95% CI, 0.77–1.10), with a single tumor of >3 cm (asHR, 1.03; 95% CI, 0.79–1.34), or with >1 tumor (asHR, 0.89; 95% CI, 0.72–1.09).ConclusionsUsing the national registry data, no difference was found in waitlist mortality and dropout for transplant candidates with HCC who received TACE versus RF ablation.     

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.     

Stereotactic Body Radiotherapy for Stage I Renal Cell Carcinoma: National Treatment Trends and Outcomes Compared to Partial Nephrectomy and Thermal Ablation

PurposeTo assess use of stereotactic body radiotherapy (SBRT) for stage I renal cell carcinoma (RCC) and compare outcomes with thermal ablation and partial nephrectomy (PN).Materials and MethodsThe 2004–2015 National Cancer Database was investigated for histopathologically proven stage I RCC treated with PN, cryoablation, radiofrequency (RF) or microwave (MW) ablation, or SBRT. Patients were propensity score–matched to account for potential confounders, including patient age, sex, race, comorbidities, tumor size, histology, grade, tumor sequence, administration of systemic therapy, treatment in academic vs nonacademic centers, treatment location, and year of diagnosis. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models.ResultsA total of 91,965 patients were identified (SBRT, n = 174; PN, n = 82,913; cryoablation, n = 5,446; RF/MW ablation, n = 3,432). Stage I patients who received SBRT tended to be older women with few comorbidities treated at nonacademic centers in New England states. After propensity score matching, a cohort of 636 patients was obtained with well-balanced confounders between treatment groups. In the matched cohort, OS after SBRT was inferior to OS after PN and thermal ablation (PN vs SBRT, hazard ratio [HR] = 0.29, 95% confidence interval [CI] 0.19–0.46, P < .001; cryoablation vs SBRT, HR = 0.40, 95% CI 0.26–0.60, P < .001; RF/MW ablation vs SBRT, HR = 0.46, 95% CI 0.31–0.67, P < .001). Compared with PN, neither cryoablation nor RF/MW ablation showed significant difference in OS (cryoablation vs PN, HR = 1.35, 95% CI 0.80–2.28, P = .258; RF/MW ablation vs PN, HR = 0.64, 95% CI 0.95–2.55, P = .079).ConclusionsCurrent SBRT protocols show lower OS compared with thermal ablation and PN, whereas thermal ablation and PN demonstrate comparable outcomes.     

γ-Glutamyltranspeptidase as a Prognostic Biomarker in Advanced Hepatocellular Carcinoma Treated with Transarterial Chemoembolization

PurposeTo evaluate the prognostic value of pretreatment serum γ-glutamyltransferase (GGT) level in patients with advanced hepatocellular carcinoma (HCC) receiving transarterial chemoembolization.Materials and MethodsThis retrospective study included 140 patients (123 male, 17 female; mean age, 56.9 y ± 12.0; range, 22.0–82.0 y) with Barcelona Clinic Liver Cancer class C HCC who received first-line conventional chemoembolization between December 2013 and March 2018. Patients were divided into low and high GGT groups based on a cutoff value calculated with a receiver operating characteristic curve. Overall survival (OS) was compared between groups by log-rank test. Univariate and multivariate survival analyses were performed.ResultsThe optimal cutoff values of GGT were 119.5 U/L in men and 175.0 U/L in women. The 6-, 9-, and 12-mo OS rates were 81.7%, 72.4%, and 62.9%, respectively, for patients in the low GGT group (n = 44) and 58.8%, 35.7%, and 28.8%, respectively, for patients in the high GGT group (n = 96; P < .001). Multivariable Cox regression analysis identified high pretreatment serum GGT level (hazard ratio [HR], 2.71; 95% confidence interval [CI], 1.67–4.40; P < .001), multiple tumors (HR, 3.05; 95% CI, 1.23–7.53; P = .02), and performance of target treatment (ie, sorafenib; HR, 0.41; 95% CI, 0.24–0.72; P = .002) or ablation (HR, 0.35; 95% CI, 0.18–0.66; P = .001) as independent prognostic factors for OS.ConclusionsPretreatment serum GGT level was an independent prognostic factor for OS in patients with advanced HCC treated with chemoembolization, suggesting that GGT is a useful prognostic biomarker for advanced HCC.     

Effectiveness of Thermal Ablation and Stereotactic Radiotherapy Based on Stage I Lung Cancer Histology

PurposeTo assess whether the effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) as initial treatments for stage I lung cancer varies depending on the histological subtype.Materials and MethodsThe 2004–2016 National Cancer Database was queried for patients with American Joint Committee on Cancer stage I lung cancer treated with TA or SBRT. Patients <18 years, those treated with surgery or chemotherapy, or those with unknown survival and follow-up were excluded. TA and SBRT patients were 1:5 propensity score matched separately for each histological subtype to adjust for confounders. Overall survival (OS) was assessed using Cox models.ResultsA total of 28,425 patients were included (SBRT, n = 27,478; TA, n = 947). TA was more likely to be used in Caucasian patients, those with more comorbidities and smaller neuroendocrine tumors (NETs) of the lower lobe, and those whose treatment had taken place in the northeastern United States. After propensity score matching, a cohort with 4,085 SBRT and 817 TA patients with balanced confounders was obtained. In this cohort, OS for TA and SBRT was comparable (hazard ratio = 1.07; 95% confidence interval,0.98–1.18; P = .13), although it varied by histological subtypes: higher OS for TA was observed in patients with non–small cell NETs (vs SBRT hazard ratio = 0.48; 95% confidence interval, 0.24–0.95; P = .04). No significant OS differences between TA and SBRT were noted for adenocarcinomas, squamous cell carcinomas, small cell carcinomas, and non-neuroendocrine large cell carcinomas (each, P > .1).ConclusionsOS following TA and SBRT for stage I lung cancer is comparable for most histological subtypes, except that OS is longer after TA in non–small cell NETs.     

Image-Guided Ablation of Recurrent or Unresectable Intrahepatic Cholangiocarcinoma

PurposeTo assess the safety and effectiveness of image-guided ablation of recurrent or unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsIn this retrospective study, 25 patients (14 women; age, 36–84 years) underwent 37 image-guided liver tumor ablation procedures to treat 47 ICCs (May 2004 to January 2022). At initial diagnosis, 20 patients had Stage 1 or 2 disease and 5 had Stage 3 or 4 disease. Before ablation, 19 (76.0%) of the 25 patients had progressed through prior treatments, including resection (n = 11), chemotherapy (n = 11), transarterial embolization (n = 3), or radiotherapy (n = 1); 6 (24.0%) of the 25 patients were treatment naïve. Ablation modality selection was based on patient and tumor characteristics and operator preference. Primary outcomes included local progression–free survival (LPFS) and overall survival (OS) after ablation. Statistical analysis included Kaplan-Meier (KM) survival analyses and Cox proportional hazards models.ResultsThe mean ablated tumor size was 2.0 cm ± 1.2 (range, 0.5–5.0 cm). The 1-, 2-, and 5-year LPFS rates were 84.0% (95% CI, 72.9–96.8), 73.0% (95% CI, 59.0–90.4), and 59.5% (95% CI, 41.6–85.1), respectively. The 1-, 2-, and 5-year secondary LPFS rates were 89.5% (95% CI, 80.2–99.9), 81.9% (95% CI, 69.4–96.6), and 75.6% (95% CI, 60.2–94.9). The 1-, 2-, and 5-year LPFS rates for tumors ≤2 cm in size were all 95.8% (95% CI, 88.2–100.0). The 1-, 2-, and 5-year OS rates were 78.5% (95% CI, 63.5–97.2), 68.4% (95% CI, 51.3–91.1), and 43.5% (95% CI, 23.5–80.5). Larger tumor size was associated with decreased time to local progression (hazard ratio, 1.93; P = .012).ConclusionsPercutaneous ablation provided favorable intermediate to long-term disease control for patients with recurrent or inoperable cholangiocarcinoma.     

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.     

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.     

Safety of Combined Yttrium-90 Radioembolization and Immune Checkpoint Inhibitor Immunotherapy for Hepatocellular Carcinoma

PurposeTo investigate the safety of yttrium-90 radioembolization in combination with checkpoint inhibitor immunotherapy for the treatment of hepatocellular carcinoma (HCC).Materials and MethodsThis single-center retrospective study included 26 consecutive patients with HCC who received checkpoint inhibitor immunotherapy within 90 days of radioembolization from April 2015 to May 2018. Patients had preserved liver function (Child-Pugh scores A–B7) and either advanced HCC due to macrovascular invasion or limited extrahepatic disease (21 patients) or aggressive intermediate stage HCC that resulted in earlier incorporation of systemic immunotherapy (5 patients). Clinical documentation, laboratory results, and imaging results at 1- and 3-month follow-up intervals were reviewed to assess treatment-related adverse events and treatment responses.ResultsThe median follow-up period after radioembolization was 7.8 months (95% confidence interval [CI], 5.6–11.8). There were no early (30-day) mortality or grades 3/4 hepatobiliary or immunotherapy-related toxicities. Delayed grades 3/4 hepatobiliary toxicities (1–3 months) occurred in 2 patients in the setting of HCC disease progression. One patient developed pneumonitis. The median overall survival from first immunotherapy was 17.2 months (95% CI, 10.9–23.4). The median overall survival from first radioembolization was 16.5 months (95% CI, 6.6–26.4). From first radioembolization, time to tumor progression was 5.7 months (95% CI, 4.2–7.2), and progression-free survival was 5.7 months (95% CI, 4.3–7.1).ConclusionsRadioembolization combined with checkpoint inhibitor immunotherapy in cases of HCC appears to be safe and causes limited treatment-related toxicity. Future prospective studies are needed to identify the optimal combination treatment protocols and evaluate the efficacy of combination therapy.     

Transcatheter CT Hepatic Arteriography Compared with Conventional CT Fluoroscopy Guidance in Percutaneous Thermal Ablation to Treat Colorectal Liver Metastases: A Single-Center Comparative Analysis of 2 Historical Cohorts

PurposeTo evaluate safety and efficacy of CT hepatic arteriography compared with conventional CT fluoroscopy guidance in percutaneous radiofrequency (RF) and microwave (MW) ablation to treat colorectal liver metastases (CRLM).Materials and MethodsThis single-center comparative, retrospective study analyzed data of 108 patients treated with 156 percutaneous ablation procedures (42 CT fluoroscopy guidance [25 RF ablation, 17 MW ablation]; 114 CT hepatic arteriography guidance [18 RF ablation, 96 MW ablation]) for 260 CRLM between January 2009 and May 2019. Local tumor progression-free survival (LTPFS) was assessed using univariate and multivariate Cox proportional hazard regression analyses. LTPFS and overall survival (OS) were estimated using the Kaplan-Meier method.ResultsThere were no complications related to the transarterial catheter procedure. CT hepatic arteriography proved superior to CT fluoroscopy regarding 2-year LTPFS (18/202 [8.9%] vs 19/58 [32.8%]; P < .001, respectively). CT hepatic arteriography versus CT fluoroscopy (hazard ratio = 0.28; 95% confidence interval, 0.15–0.54; P < .001) and MW ablation versus RF ablation (hazard ratio = 0.52; 95% confidence interval, 0.24–1.12; P = .094) were positive predictors for longer LTPFS. Multivariate analysis revealed that CT hepatic arteriography versus CT fluoroscopy (hazard ratio = 0.41; 95% confidence interval, 0.19–0.90; P = .025) was associated with a significantly superior LTPFS. OS was similar between the 2 cohorts (P = .3).ConclusionsWhile adding procedure time and marginal patient burden, transcatheter CT hepatic arteriography–guided ablation was associated with increased local disease control and superior LTPFS compared with conventional CT fluoroscopy. CT hepatic arteriography represents a safe and valid alternative to CT fluoroscopy, as it reduces the number of repeat ablations required without adding risk or detrimental effect on survival.     

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.     

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.     

Prognostic Factors for Local Recurrence after Cryoablation of Desmoid Tumors

PurposeTo determine the risk factors for local of adult patients treated for desmoid tumors by cryoablation.Materials and MethodsEighty-four patients treated for nonabdominopelvic desmoid tumors by cryoablation from July 2012 to July 2020 were included in a retrospective study. The population was composed of 64 women (76.19%) and 20 men (23.81%), aged from 16 to 75 years (median, 35 years ± 14.25). Each patient underwent preprocedural gadolinium-enhanced magnetic resonance imaging and was followed up to 36 months with the same technique. Clinical features, such as tumor size and previous treatment, epidemiological features, and the technical parameters of cryoablation, were studied.ResultsLocal relapse was found in 19 (22.62%) of 84 patients. The 12-, 24-, and 36-month progression-free survival rates were 89% (95% confidence interval [CI], 79–94), 74% (95% CI, 60–83), and 68% (95% CI, 53–79), respectively. In univariate analysis, significant prognostic factors associated with local recurrence were non–abdominal wall location (P = .042), debulking strategy (P = .0105), risk of visceral injury (P = .034) or peripheral nerve injury during cryoablation (P = .033), previous radiation therapy (P = .043), and treatment before 2016 (P = .008). In multivariate analysis, abdominal wall tumors displayed the best outcome, whereas the neck and trunk showed a high rate of recurrence (hazard ratio, 7.307 [95% CI, 1.396–38.261]).ConclusionsThe local recurrence of desmoid tumors after cryoablation depends on a number of prognostic factors, in particular, a non–abdominal wall location of the tumor and previous local treatment such as surgery or radiation therapy.     

Safety and Effectiveness of Yttrium-90 Radioembolization around the Time of Immune Checkpoint Inhibitors for Unresectable Hepatic Metastases

PurposeTo assess the safety and effectiveness of yttrium-90 radioembolization and checkpoint inhibitor immunotherapy within a short interval for the treatment of unresectable hepatic metastases.Materials and MethodsThis single-institution retrospective study included 22 patients (12 men; median age, 65 y ± 11) with unresectable hepatic metastases and preserved functional status (Eastern Cooperative Oncology Group performance status 0/1) who received immunotherapy and radioembolization within a 15-month period (median, 63.5 d; interquartile range, 19.7–178.2 d) from February 2013 to March 2018. Primary malignancies were uveal melanoma (12 of 22; 54.5%), soft tissue sarcoma (3; 13.6%), cutaneous melanoma (3; 14%), and others (4; 18.2%). Studies were reviewed to March 2019 to assess Common Terminology Criteria for Adverse Events grade 3/4 toxicities, disease progression, and death.ResultsThere were no grade 4 toxicities within 6 mo of radioembolization. Grade 3 hepatobiliary toxicities occurred in 3 patients (13.6%) within 6 months, 2 from rapid disease progression and 1 from a biliary stricture. Two patients (9.1%) experienced clinical toxicities, including grade 4 colitis at 6 months and hepatic abscess at 3 months. Median overall survival (OS) from first radioembolization was 20 mo (95% confidence interval [CI], 12.5–27.5 mo), and median OS from first immunotherapy was 23 months (95% CI, 15.9–30.1 mo). Within the uveal melanoma subgroup, the median OS from first radioembolization was 17.0 months (95% CI, 14.2–19.8 mo). Median time to progression was 7.8 months (95% CI, 3.3–12.2 mo), and median progression-free survival was 7.8 mo (95% CI, 3.1–12.4 mo).ConclusionsCheckpoint immunotherapy around the time of radioembolization is safe, with a low incidence of toxicity independent of primary malignancy.     

Yttrium-90 Radiation Segmentectomy of Hepatocellular Carcinoma: A Comparative Study of the Effectiveness,Safety, and Dosimetry of Glass-Based versus Resin-Based Microspheres

PurposeTo evaluate the differences in safety, effectiveness, and dosimetry between glass-based and resin-based ablative yttrium-90 (⁹⁰Y) transarterial radioembolization (TARE) of hepatocellular carcinoma (HCC).Materials and MethodsUsing the modified Response Evaluation Criteria in Solid Tumors and Common Terminology Criteria for Adverse Events, both tumor response and adverse events (AEs) were assessed at 3 months after ⁹⁰Y-TARE. Post procedure ⁹⁰Y-bremsstrahlung single-photon emission computed tomography/computed tomography voxel-based dosimetry analysis was used to create tumor dose (TD) and normal tissue dose (NTD) volume histograms, and to calculate tumor particle loading and specific activity. The TD and NTD receiver operating characteristic curves evaluated the dose threshold able to predict objective (partial or complete) and complete tumor responses in addition to any-grade and grade ≥3 AE incidences. The chi-square test and Student t-test were used to assess variable differences where appropriate.ResultsBetween 2019 and 2020, 81 patients with HCC (20 in the resin-based cohort and 61 in the glass-based cohort) underwent ablative ⁹⁰Y-TARE. The resin-based cohort had more males (89% vs 65%, P = .03), lower tumor-to-normal ratio (1.81 ± 0.39 vs 2.22 ± 0.94, P = .03), higher tumor particle loading (40,172 particles/mL ± 28,039 vs 17,081 particles/mL ± 12,555, P = .0001), lower specific activity (158 Bq/particle ± 3 vs 1,058 Bq/particle ± 331, P = .001), and lower mean TD (308 Gy ± 210 vs 794 Gy ± 523, P = .0002) than the glass-based cohort. No significant differences in baseline characteristics or posttreatment AEs were noted. The overall objective and complete response rates were 85% (95% resin-based vs 82% glass-based; P = .1) and 65% (95% resin-based vs 56% glass-based; P = .003), respectively. The mean TD thresholds able to predict the objective and complete responses were 176 Gy and 247 Gy for resin-based radioembolization and 290 Gy and 481 Gy for glass-based radioembolization, respectively. A maximum NTD of 999 Gy predicted any-grade AEs in glass-based ablative ⁹⁰Y-TARE.ConclusionsCompared with glass-based ablative ⁹⁰Y-TARE, resin-based ablative ⁹⁰Y-TARE can offer comparable safety and effectiveness profiles for patients with HCC. The impact of the significantly different tumor particle loading, particle specific activities, and delivered TDs on tumor response outcomes merits further investigation.     

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.     

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.     

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.     

Hepatic Artery Infusion Chemotherapy Using Fluorouracil,Leucovorin, and Oxaliplatin versus Transarterial Chemoembolization as Initial Treatment for Locally Advanced Hepatocellular Carcinoma: A Propensity Score–Matching Analysis

PurposeTo compare the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) with a modified fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) regimen with that of transarterial chemoembolization as a locoregional treatment for patients with locally advanced hepatocellular carcinoma (HCC).MethodsThis retrospective study included adult patients with locally advanced HCC who received first-line treatment with either HAIC-mFOLFOX or conventional transarterial chemoembolization monotherapy from January 2015 to December 2016. The outcomes, including tumor response rates, evaluated via imaging assessment using the modified response evaluation criteria in solid tumors; overall survival; progression-free survival; and safety, were compared. The propensity score–matching methodology was used to reduce the influence of confounding factors on the outcomes.ResultsThe study included 131 patients with locally advanced HCC who underwent transarterial chemoembolization and 101 who received HAIC-mFOLFOX as initial treatment. After propensity score matching (n = 67 in each group), patients who received HAIC-mFOLFOX had a higher objective response rate (43.3% vs 13.4%, P = .001), longer median overall survival (13.9 vs 6.0 months, P < .001), and longer median progression-free survival (6.4 vs 2.8 months, P = .001) than those who underwent transarterial chemoembolization. The survival benefit with HAIC-mFOLFOX was strengthened in patients with HCC with vascular invasion (hazard ratio: 0.379; 95% confidence interval: 0.237–0.607). HAIC-mFOLFOX was associated with lower incidences of severe adverse events (8.9% vs 22.9%) and liver toxicity than transarterial chemoembolization.ConclusionsCompared with transarterial chemoembolization, HAIC-mFOLFOX is a potentially safer and more effective locoregional therapy for patients with locally advanced HCC.