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.     

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.     

Transarterial Yttrium-90 Radioembolization for Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review and Meta-Analysis

PurposeTo investigate the overall efficacy and survival profile of yttrium-90 (⁹⁰Y) radioembolization for unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsA systematic literature review and meta-analysis was completed using a random-effects model. Studies describing the use of ⁹⁰Y for unresectable ICC were included. The disease control rate (DCR), downstaged-to-resectable rate, cancer antigen 19-9 (CA19-9) response rate, pooled median overall survival (OS), pooled median progression-free survival (PFS), and mean reported survival rates ranging from 3 to 36 months were evaluated.ResultsTwenty-one studies detailing a total of 921 patients were included. The overall DCR was 82.3% (95% confidence interval [CI], 76.7%–87.8%; I² = 81%). In 11% of the cases, patients were downstaged to being surgically resectable (95% CI, 6.1%–15.9%; I² = 78%). The CA19-9 response rate was 67.2% (95% CI, 54.5%–79.8%; I² = 60%). From the time of radioembolization, PFS was 7.8 months (95% CI, 4.2–11.3 months; I² = 94%) and median OS was 12.7 months (95% CI, 10.6–14.8 months; I² = 62%). Lastly, the mean overall reported survival proportions were 84% at 3 months (standard deviation [SD], 10%), 69% at 6 months (SD, 16%), 47% at 12 months (SD, 19%), 31% at 18 months (SD, 21%), 30% at 24 months (SD, 19%), 21% at 30 months (SD, 27%), and 5% at 36 months (SD, 7%).ConclusionsRadioembolization with ⁹⁰Y for unresectable ICC results in substantial downstaging, disease control, and survival.     

Yttrium-90 Radiation Segmentectomy in Oligometastatic Secondary Hepatic Malignancies

PurposeTo evaluate the safety and efficacy of yttrium-90 (⁹⁰Y) radiation segmentectomy (RS) in the treatment of oligometastatic secondary hepatic malignancies.Materials and MethodsThis institutional review board–approved retrospective study evaluated 16 patients with oligometastatic secondary hepatic malignancies who were treated with RS. The median patient age was 61.9 years (range, 38.6–85.7 years). Of the 16 patients, 11 (68.8%) presented with solitary lesions. The median index tumor size was 3.1 cm (95% CI, 2.3–3.9). Primary outcomes were evaluation of clinical and biochemical toxicities using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0, and imaging response using Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary outcomes were time to progression (TTP) and overall survival (OS) as estimated by the Kaplan-Meier method.ResultsClinical Grade 3 toxicities were limited to 1 (6.7%) patient who experienced fatigue, abdominal pain, nausea, and vomiting. Biochemical Grade 3 toxicities occurred in 1 (6.7%) patient who experienced lymphopenia. No Grade 4 clinical or biochemical toxicities were identified. Disease control was achieved in 14 (93.3%) of 15 patients. The median TTP of the treated tumor was 72.9 months (95% CI, 11.2 to no estimate). The median OS was 60.9 months (95% CI, 24.7 to no estimate).Conclusions⁹⁰Y RS displayed an excellent safety profile and was effective in achieving a high disease control rate in the treatment of oligometastatic secondary hepatic malignancies.     

Predictors of Survival after Yttrium-90 Radioembolization of Chemotherapy-Refractory Hepatic Metastases from Breast Cancer

PurposeTo determine predictors of survival after transarterial radioembolization of hepatic metastases from breast cancer.Materials and MethodsTwenty-four patients with chemotherapy-refractory hepatic metastases from breast cancer who underwent radioembolization from 2013 to 2018 were evaluated based on various demographic and clinical factors before and after treatment. Overall survival (OS) was estimated by Kaplan–Meier method. Log-rank analysis was performed to determine predictors of prolonged OS from the time of first radioembolization and first hepatic metastasis diagnosis.ResultsMedian OS times were 35.4 and 48.6 months from first radioembolization and time of hepatic metastasis diagnosis, respectively. Radioembolization within 6 months of hepatic metastasis diagnosis was a positive predictor of survival from first radioembolization, with median OS of 38.9 months vs 22.1 months for others (P = .033). Estrogen receptor (ER)–positive status predicted prolonged survival (38.6 months for ER⁺ vs 5.4 months for ER⁻; P = .005). The presence of abdominal pain predicted poor median OS: 12.8 months vs 38.6 months for others (P < .001). The presence of ascites was also a negative predictor of OS (1.7 months vs 35.4 months for others; P = .037), as was treatment-related grade ≥ 2 toxicity at 3 months (5.4 months vs 38.6 months for others; P = .017).ConclusionsIn patients with metastatic breast cancer, radioembolization within 6 months of hepatic metastasis diagnosis and ER⁺ status appear to be positive predictors of prolonged survival. Conversely, baseline abdominal pain, baseline ascites, and treatment-related grade ≥ 2 toxicity at 3 months after treatment appear to be negative predictors of OS.     

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.     

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.     

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.     

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.     

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.     

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.     

Safety and Efficacy of Segmental Yttrium-90 Radioembolization for Hepatocellular Carcinoma after Transjugular Intrahepatic Portosystemic Shunt Creation

PurposeTo evaluate safety and efficacy of segmental yttrium-90 (Y90) radioembolization for hepatocellular carcinoma (HCC) after transjugular intrahepatic portosystemic shunt (TIPS) placement. The hypothesis was liver sparing segmental Y90 for HCC after TIPS would provide high antitumor response with a tolerable safety profile.Materials and MethodsThis single-arm retrospective study included 39 patients (16 women, 23 men) with ages 49–81 years old who were treated with Y90. Child-Pugh A/B liver dysfunction was present in 72% (28/39) with a median Model for End-stage Liver Disease score of 18 (95% confidence interval, 16.4–19.4). Primary outcomes were clinical and biochemical toxicities and antitumor imaging response by World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. Secondary outcomes were orthotopic liver transplantation (OLT), time to progression (TTP), and overall survival (OS) estimates by the Kaplan-Meier method.ResultsThe 30-day mortality was 0%. Grade 3+ clinical adverse events and grade 3+ hyperbilirubinemia occurred in 5% (2/39) and 0% (0/39), respectively. Imaging response was achieved in 58% (22/38, WHO criteria) and 74% (28/38, EASL criteria), respectively. Median TTP was 16.1 months for any cause and 27.5 months for primary index lesions. OLT was completed in 88% (21/24) of listed patients at a median time of 6.1 months (range, 0.9–11.7 months). Median OS was 31.6 months and 62.9 months censored and uncensored to OLT, respectively.ConclusionsSegmental Y90 for HCC appears safe and efficacious in patients after TIPS. Preserved transplant eligibility suggests that Y90 is a useful tool for bridging these patients to liver transplantation.     

Sintilimab plus Bronchial Arterial Infusion Chemotherapy/Drug-Eluting Embolic Chemoembolization for Advanced Non–Small Cell Lung Cancer: A Preliminary Study of 10 Patients

PurposeTo evaluate the short-term efficacy and safety of immunotherapy with sintilimab combined with bronchial arterial infusion (BAI) chemotherapy/drug-eluting embolic (DEE) bronchial arterial chemoembolization (BACE) for advanced non–small cell lung cancer (NSCLC).Materials and MethodsTen patients with advanced NSCLC were treated with sintilimab plus BAI/DEE-BACE between December 2019 and November 2020 and retrospectively evaluated. The Response Evaluation Criteria in Solid Tumors version 1.1 was applied to evaluate the treatment response. The local tumor control duration, progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier analysis.ResultsAt 30 days after the last multimodal treatment, complete response, partial response, and stable disease were recorded in 1 (10%), 7 (70%), and 2 (20%) patients, respectively, for an objective response rate of 80% and a disease control rate of 100%. No patient experienced progressive disease. The median duration of local tumor control was 8.0 months (95% CI, 6.2–9.7 months). The median PFS and OS were 11.0 months (95% CI, 6.9–15.1 months) and 8.0 months (95% CI, 5.5–10.5 months), respectively. Two cases of Grade III adverse events related to medications were reported.ConclusionsSintilimab combined with BAI/DEE-BACE for patients with advanced NSCLC appears to be safe and feasible. Compared with previous studies on BAI/DEE-BACE, the addition of immunotherapy may improve survival.     

The Safety and Effectiveness of Hepatic Transarterial Embolic Locoregional Therapy in Patients with Contraindications to Hepatectomy after Portal Vein Embolization

The safety and effectiveness of hepatic transarterial embolic locoregional therapy (LRT) was assessed, including transarterial chemoembolization (TACE) and transarterial radioembolization (TARE), in patients who underwent portal vein embolization (PVE) before major hepatectomy in whom surgery was then contraindicated. Adverse events (AEs) were graded according to the Society of Interventional Radiology classification of AEs. Tumor response was assessed based on the Response Evaluation Criteria In Solid Tumors 1.1. Overall survival (OS) and progression-free survival (PFS) were estimated. Fifteen patients underwent 37 transarterial LRTs (25 TACEs, 11 TAREs, and 1 bland embolization), most (73%) with hepatocellular carcinoma. Eleven AEs occurred in 7 patients, including 2 Grade 3/5 (severe) and 2 Grade 4/5 (life-threatening) events. The best response was partial response in 4 (27%) and stable disease in 10 (66%) patients. The median OS and PFS were 42 (95% CI, 35–49 months) and 33 months (95% CI, 24–42 months), respectively. In conclusion, hepatic transarterial LRT can be considered as a therapeutic option in patients with contraindicated liver surgery after PVE.     

Safety and Efficacy of Locoregional Treatment during Immunotherapy with Nivolumab for Hepatocellular Carcinoma: A Retrospective Study of 41 Interventions in 29 Patients

PurposeTo assess the safety of locoregional treatment (LRT) combined with nivolumab for intermediate and advanced hepatocellular carcinoma (HCC).Materials and MethodsA single-center retrospective review included 29 patients undergoing 41 LRTs—transarterial chemoembolization or yttrium-90 transarterial radioembolization—60 days before or concurrently with nivolumab. Demographic, clinical, and laboratory values and adverse events were reviewed before and after nivolumab initiation and after each LRT. Treatment response and time to progression were assessed using Modified Response Evaluation Criteria in Solid Tumors. Clinical events, including nivolumab termination, death, and time of last follow-up, were assessed.ResultsOver a median nivolumab course of 8.1 months (range, 1.0–30) with a median of 14.2 2-week cycles (range, 1–53), predominantly Child–Pugh A (22/29) patients—12 Barcelona Clinic Liver Cancer (BCLC) B and 17 BCLC C—underwent 20 transarterial chemoembolization and 21 transarterial radioembolization LRTs at a median of 67 days (range, 48–609) after nivolumab initiation. Ten patients underwent multiple LRTs. During a median follow-up of 11.5 months (range, 1.8–35.1), no grade III/IV adverse events attributable to nivolumab were observed. There were five instances of grade III/IV hypoalbuminemia or hyperbilirubinemia within 3 months after LRT. There were no nivolumab-related deaths, and 30-day mortality after LRT was 0%.ConclusionsLRTs performed concurrently with nivolumab immunotherapy demonstrate an acceptable safety profile in patients with intermediate and advanced HCC.     

Safety and Efficacy of Arterially Directed Liver Therapies in the Treatment of Hepatic Metastatic Ovarian Cancer: A Retrospective Single-Institution Study

PurposeTo evaluate the safety and efficacy of 2 locoregional therapies (LRTs) including hepatic artery embolization (HAE) and transarterial radioembolization (TARE) in the treatment of patients with metastatic ovarian cancer to the liver.Material and MethodsFrom October 2010 to May 2019, the data of 15 consecutive patients (median age, 54 years ± 9.8; range, 35–78 years) with hepatic metastatic ovarian cancer who were treated with either HAE (n = 6; 40%) or TARE (n = 9; 60%) were reviewed. The most common histopathologic type was epithelial ovarian carcinoma (80%). The most common chemotherapy regimens used prior to embolization included carboplatin, paclitaxel, cisplatin, and bevacizumab. Patients received a mean of 4 lines ± 3 (range, 1–9) of chemotherapy. All patients with serous carcinoma were resistant to platinum at the time of embolization. Indications for embolization were progression of disease to the liver while receiving chemotherapy in 14 (93.3%) patients and palliative pain control in 1 patient.ResultsThe overall response rates at 1, 3, and 6 months were 92.4%, 85.6%, and 70%, respectively. Median overall survival from the time of LRT was 9 (95% confidence interval [CI], 4–14) months. Median local tumor progression was 6.4 months ± 5.03 (95% CI, 3.3–9.5). No grade 3–5 adverse events were detected in either group.ConclusionsHAE and TARE were well tolerated in patients with metastatic ovarian cancer to the liver and possibly ensured prolonged disease control in heavily treated, predominantly in patients resistant to platinum. Larger numbers are needed to verify these data.     

Survival and Toxicities after Yttrium-90 Transarterial Radioembolization of Cholangiocarcinoma in the RESiN Registry

PurposeTo report outcomes in patients with intrahepatic cholangiocarcinoma treated with yttrium-90 resin microspheres (transarterial radioembolization [TARE]) from a multicenter, prospective observational registry.Materials and MethodsNinety-five patients (median age, 67 years [interquartile range {IQR}, 59–74]; 50 men) were treated in 27 centers between July 2015 and August 2020. Baseline demographic characteristics included imaging findings, performance status, and previous systemic or locoregional treatments. Dosimetry method was tracked. Overall survival (OS) and progression-free survival were calculated using the Kaplan-Meier method. The best imaging response was calculated using the Response Evaluation Criteria in Solid Tumors v1.1. Grade ≥3 toxicities were assessed using Common Terminology Criteria for Adverse Events v5. Cox regression analysis was performed.ResultsFifty-two of 86 (60%) patients had multifocal tumors, and 24/89 (27%) had extrahepatic tumors. The median index tumor diameter was 7.0 cm (IQR, 4.9–10 cm). The activity calculation method was reported in 59/95 (62%) patients, with body surface area being the most frequently used method (45/59, 76%). Median OS for the cohort was 14 months (95% confidence interval, 12–22). OS at 3, 6, 12, and 24 months was 94%, 80%, 63%, and 34%, respectively. Median OS was longer in patients without cirrhosis (19.1 vs 12.2 months, P = .05). Cirrhosis, previous chemotherapy (OS, 19.1 vs 10.6 months for treatment-naïve; P = .07), and imaging response at 6 months (OS, 16.4 vs 9.5 months for no response; P = .06) underwent regression analysis. Imaging response predicted OS at regression (hazard ratio, 0.39; P = .008). Grade 3–4 bilirubin toxicities were noted in 5 of 72 (7%) patients. Grade 3 albumin toxicity was noted in 1 of 72 (1.4%) patients.ConclusionsObjective response at 6 months predicted longer OS after TARE for intrahepatic cholangiocarcinoma. The incidence of liver function toxicity was <10%.     

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 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.     

Intra-Arterial Therapy for Unresectable Colorectal Liver Metastases: A Meta-Analysis

PurposeTo evaluate the efficacy of hepatic arterial infusion (HAI), conventional transarterial chemoembolization, drug-eluting embolic transarterial chemoembolization (DEE-TACE), transarterial radioembolization, and their combinations with systemic chemotherapy (SCT) for unresectable colorectal liver metastases.MethodsA search was conducted on Embase, Scopus, PubMed, and Web of Science for prospective nonrandomized studies and randomized controlled trials (RCTs) from inception to June 20, 2020. Survival data of patients were recovered from original Kaplan-Meier curves by exploiting a graphical reconstructive algorithm. One-stage meta-analyses were conducted for the median overall survival (OS), survival rates (SRs), and restricted mean survival time (RMST), whereas two-stage meta-analyses of proportions were conducted to determine response rates (RRs) and conversion to resection rates (CRRs).ResultsA total of 71 prospective nonrandomized studies and 21 RCTs were identified, comprising 6,695 patients. Among patients treated beyond the first-line, DEE-TACE + SCT (n = 152) had the best survival outcomes of median OS of 26.5 (95% confidence interval [CI], 22.5–29.1) months and a 3-year RMST of 23.6 (95% CI, 21.8–25.5) months. Upon further stratification by publication year, DEE-TACE + SCT appeared to consistently have the highest pooled SRs at 1 year (81.9%) and 2 years (66.1%) in recent publications (2015–2020). DEE-TACE + SCT and HAI + SCT had the highest pooled RRs of 56.7% (I² = 0.90) and 62.6% (I² = 0.87) and pooled CRRs of 35.5% (I² = 0.00) and 30.3% (I² = 0.80), respectively.ConclusionsAlbeit significant heterogeneity, the paucity of high-quality evidence, and the noncomparative nature of all analyses, the overall evidence suggests that patients treated with DEE-TACE + SCT have the best oncological outcomes and greatest potential to be converted for resection.