Radiation Emission from Patients Treated with Holmium-166 Radioembolization

PurposeTo assess the radiation exposure to individuals coming from patients after treatment with holmium-166 (¹⁶⁶Ho) microspheres.Materials and MethodsHolmium-166 radioembolization (RE) with escalating whole-liver doses of 20 Gy, 40 Gy, 60 Gy, and 80 Gy was administered to 15 patients. Exposure rates (μSv/h) from patients were measured at 1.0 m distance from a lateral and frontal position at 0, 3, 6, 24, and 48 hours after infusion. The total effective dose equivalent (TEDE) to a maximally exposed contact was calculated in accordance with guidelines of the U.S. Nuclear Regulatory Commission (NRC). Results were extrapolated to a whole-liver dose of 60 Gy used in future treatments.ResultsThe median exposure rate at discharge, 48 hours after infusion, measured from a lateral position was 26 μSv/h (range, 7–45 μSv/h). Extrapolated to a whole-liver dose of 60 Gy, none of the exposure rates for the NRC contact scenario, at any time, frontal or lateral, would lead to a TEDE > 5 mSv; all patients may be released directly after treatment. Release after 6 hours is possible without contact restrictions for patients who received up to 7 GBq.ConclusionsThe TEDE to a contact of patients treated with ¹⁶⁶Ho RE would not exceed the NRC limit of 5 mSv. Contact restrictions 6 hours after treatment are unnecessary for infused activities < 7 GBq.     

Holmium-166 Radioembolization in Hepatocellular Carcinoma: Feasibility and Safety of a New Treatment Option in Clinical Practice

CardioVascular and Interventional Radiology - To investigate clinical feasibility, technical success and toxicity of 166Ho-radioembolization (166Ho-RE) as new approach for treatment of...     

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.     

Holmium-166-DTPA as a liquid source for endovascular brachytherapy

Liquid radiation sources with β emitters have advantages of accurate positioning and uniform dose distribution to the vessel walls to prevent the restenosis of coronary artery. As a liquid radiation source, ¹⁶⁶Ho-DTPA was prepared and evaluated its in-vivo pharmacokinetic behavior through animal studies.

¹⁶⁶Ho-DTPA was prepared by simple mixing the Holmium with DTPA at room temperature. The radiolabelling yield was 100% when the DTPA/Holmium molar ratio was >2. Radiolabelling of ¹⁶⁶Ho-DTPA was not dependent on the pH range of 1.7–7.5. High radiochemical stability (>98%) was maintained over a period of 6 hours even with a radioactivity (11.1 GBq/12 mg of DTPA) stored at room temperature.

Biodistribution of ¹⁶⁶Ho-DTPA in rats and gamma camera images in rabbits showed that ¹⁶⁶Ho-DTPA was quickly excreted via the urinary system. The average of T_max and T_1/2 of ¹⁶⁶Ho-DTPA in the kidneys of rabbits were 3.71 ± 1.18 min and 9.15 ± 3.15 min. ¹⁶⁶Ho-DTPA is a potential liquid radiation source for radiation brachytherapy to prevent the restenosis of the coronary artery using a liquid-filled balloon.     

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.     

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.     

Yttrium-90 Radioembolization for Intrahepatic Cholangiocarcinoma: Safety,Response, and Survival Analysis

PurposeTo present data on safety, antitumoral response, and survival following yttrium-90 (⁹⁰Y) radioembolization for patients with unresectable intrahepatic cholangiocarcinoma (ICC).Materials and MethodsThe present study expands on the cohort of 24 patients with ICC described in a pilot study, and includes 46 patients treated with ⁹⁰Y radioembolization at a single institution during an 8-year period. Via retrospective review of a prospectively collected database, patients were stratified by performance status, tumor distribution (solitary or multifocal), tumor morphology (infiltrative or peripheral), and presence/absence of portal vein thrombosis. Primary endpoints included biochemical and clinical toxicities, and secondary endpoints included imaging response (World Health Organization [WHO] and European Association for the Study of Liver Disease [EASL] criteria) and survival. Uni-/multivariate analyses were performed.ResultsNinety-two treatments were performed, with a mean of two per patient. Fatigue and transient abdominal pain occurred in 25 patients (54%) and 13 patients (28%), respectively. Treatment-related gastroduodenal ulcer developed in one patient (2%). WHO imaging findings included partial response (n = 11; 25%), stable disease (n = 33; 73%), and progressive disease (n = 1; 2%). EASL imaging findings included partial/complete response (n = 33; 73%) and stable disease (n = 12; 27%). Survival varied based on presence of multifocal (5.7 mo vs 14.6 mo), infiltrative (6.1 mo vs 15.6 mo), and bilobar disease (10.9 mo vs 11.7 mo). Disease was converted to resectable status in five patients, who successfully underwent curative (ie, R0) resection.ConclusionsRadioembolization with ⁹⁰Y is safe and demonstrates antitumoral response and survival benefit in select patients with ICC. Results are most pronounced in patients with solitary tumors, for whom conversion to curative resection is possible.     

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.     

Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study

Purpose

To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC).

Yttrium-90 Radioembolization Is Cost Effective in Intrahepatic Cholangiocarcinoma: A SEER Medicare Population Study

Purpose

To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database.

Yttrium-90 Radioembolization for Unresectable Standard-chemorefractory Intrahepatic Cholangiocarcinoma: Survival, Efficacy, and Safety Study

Purpose

To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC).

Methods

Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan–Meier estimator by the log rank test.

Results

Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374–1130] and 345 ± 128 (95 % CI 95–595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78–822) and 345 ± 227 (95 % CI 0–790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0–1010) days versus 345 ± 117 (95 % CI 115–575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively.

Conclusion

Y90 radioembolization is effective for unresectable standard-chemorefractory 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.     

Transarterial Hepatic Yttrium-90 Radioembolization in Patients with Unresectable Intrahepatic Cholangiocarcinoma: Factors Associated with Prolonged Survival

Introduction

In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 (⁹⁰Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS).

Methods

Patients with unresectable ICC were treated with ⁹⁰Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS.

Results

Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3?months. The median OS was 22?months posttreatment and 43.7?months postdiagnosis. Median TTP was 9.8?months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1?months; TTP: 17.5, 6.9, and 2.4?months), tumor burden ??25% (OS: 26.7 vs. 6?months; TTP: 17.5 vs. 2.3?months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7?months; TTP: 31.9, 9.8 vs. 2.5?months), respectively (P?<?0.001).

Conclusions

Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.     

胆管细胞型肝癌的CT表现

目的 :探讨胆管细胞型肝癌的CT表现。材料和方法 :回顾性分析经手术及病理证实的 2 6例胆管细胞型肝癌的CT资料。所有患者均做了CT平扫及双期增强扫描 ,其中 8例另做了延迟扫描。结果 :CT主要表现有 :( 1)平扫 :单发性体积较大的肿块 ,边界不清 ,瘤内及瘤周可见扩张的胆管。 ( 2 )动脉期 :早期边缘不规则环状明显增强。 ( 3 )门脉期 :病灶进一步呈网格状增强 ,常略低于正常肝实质增强。 ( 4 )延迟期 :病灶不均匀向心性增强 ,略高于正常肝实质。结论 :胆管细胞型肝癌的CT表现有特征性 ,在与肝内其他常见的占位性病变的鉴别方面有重要价值。     

肝内胆管细胞癌的CT表现

目的分析胆管细胞癌的CT表现,提高对胆管细胞癌的认识。方法回顾性分析经病理证实的21例胆管细胞癌的CT表现。结果CT平扫所有病例均为单发低密度灶。CT增强扫描21例不均匀轻度强化,其中4例出现大片无强化低密度区,部分边缘强化,2例病灶延迟强化,17例肝内胆管扩张。结论CT是胆管细胞癌的重要影像检查方法,不均匀强化病灶内可见胆管扩张是胆管细胞癌的重要征象。     

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.     

Evaluation of the Safety and Feasibility of Same-Day Holmium-166 -Radioembolization Simulation and Treatment of Hepatic Metastases

PurposeTo evaluate the safety and feasibility of same-day treatment, including the simulation procedure for assessment of intrahepatic and extrahepatic distribution of the microspheres, with holmium-166 (¹⁶⁶Ho)-radioembolization.Materials and MethodsThis was a secondary analysis of patients included in the 4 prospective studies (HEPAR I, HEPAR II, HEPAR PLuS, and SIM) on ¹⁶⁶Ho-radioembolization. The technical success rate of the same-day treatment protocol, defined as the number of patients who completed the same-day treatment, was measured. Total in-room time, duration of the scout procedure, time to imaging, and duration of the treatment procedure were recorded. Reasons for discontinuation or adjustment of treatment were identified. Adverse events that occurred during the treatment day were recorded.ResultsOne hundred five of 120 scheduled patients completed the same-day treatment with ¹⁶⁶Ho-radioembolization (success rate, 88%). After the simulation procedure, treatment was cancelled in 15 patients because of extrahepatic deposition (n = 8), suboptimal tumor targeting (n = 1), unanticipated vascular anatomy (n = 5), and dissection (n = 1). In another 14 patients, the treatment plan was adjusted. The median total procedure time (ie, simulation, imaging, and treatment) was 6:39 hours:minutes (range, 3:58–9:17 hours:minutes). Back pain was a major same-day treatment-related complaint (n = 28).Conclusion¹⁶⁶Ho-radioembolization as a same-day treatment procedure is feasible in most selected patients, although treatment was adjusted in 12% of patients and cancelled in 12% of patients. This approach might be beneficial for a select patient population, such as patients needing a radiation segmentectomy.