Radioembolization with 90Y glass microspheres for the treatment of unresectable metastatic liver disease from chemotherapy-refractory gastrointestinal cancers: final report of a prospective pilot study.
ABSTRACT: BACKGROUND:This prospective pilot single-institution study was undertaken to document the feasibility, safety, and efficacy of radioembolization of liver-dominant metastatic gastrointestinal cancer using 90Y glass microspheres. METHODS:Between June 2010 and October 2013, 42 adult patients (26 men, 16 women; median age 60 years) with metastatic chemotherapy-refractory unresectable colorectal (n=21), neuroendocrine (n=11), intrahepatic bile duct (n=7), pancreas (n=2), and esophageal (n=1) carcinomas underwent 60 lobar or segmental administrations of 90Y glass microspheres. Data regarding clinical and laboratory adverse events (AE) were collected prospectively for up to 5.5 years after radioembolization. Radiographic responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. Time to maximum response, response duration, progression-free survival (PFS) (hepatic and extrahepatic), and overall survival (OS) were measured. RESULTS:Median target dose and activity were 109.4 Gy and 2.6 GBq per treatment session, respectively. Majority of clinical AE were grade 1 or 2 in severity. Patients with colorectal cancer had hepatic objective response rate (ORR) of 25% and a hepatic disease control rate (DCR) of 80%. Median PFS and OS were 1.0 and 4.4 months, respectively. Patients with neuroendocrine tumors (NET) had hepatic ORR and DCR of 73% and 100%, respectively. Median PFS was 8.9 months for this cohort. DCR and median PFS and OS for patients with cholangiocarcinoma were 86%, 1.1 months, and 6.7 months, respectively. CONCLUSIONS:90Y glass microspheres device has a favorable safety profile, and achieved prolonged disease control of hepatic tumor burden in a subset of patients, including all patients enrolled in the neuroendocrine cohort.
Project description:<h4>Background</h4>The safety and tolerability of sequential radioembolization-sorafenib therapy is unknown. An open-label, single arm, investigator-initiated Phase II study (NCT0071279) was conducted at four Asia-Pacific centers to evaluate the safety and efficacy of sequential radioembolization-sorafenib in patients with hepatocellular carcinoma (HCC) not amenable to curative therapies.<h4>Methods</h4>Sorafenib (400 mg twice-daily) was initiated 14 days post-radioembolization with yttrium-90 (90Y) resin microspheres given as a single procedure. The primary endpoints were safety and tolerability and best overall response rate (ORR) using RECIST v1.0.Secondary endpoints included: disease control rate (complete [CR] plus partial responses [PR] and stable disease [SD]) and overall survival (OS).<h4>Results</h4>Twenty-nine patients with Barcelona Clinic Liver Cancer (BCLC) stage B (38%) or C (62%) HCC received a median of 3.0 GBq (interquartile range, 1.0) 90Y-microspheres followed by sorafenib (median dose/day, 600.0 mg; median duration, 4.1 months). Twenty eight patients experienced ?1 toxicity; 15 (52%) grade ?3. Best ORR was 25%, including 2 (7%) CR and 5 (18%) PR, and 15 (54%) SD. Disease control was 100% and 65% in BCLC stage B and C, respectively. Two patients (7%) had sufficient response to enable radical therapy. Median survivals for BCLC stage B and C were 20.3 and 8.6 months, respectively.<h4>Conclusions</h4>This study shows the potential efficacy and manageable toxicity of sequential radioembolization-sorafenib.<h4>Trial registration</h4>ClinicalTrials.gov NCT00712790.
Project description:Yttrium-90 (90Y) radioembolization is a minimally invasive procedure increasingly used for advanced liver cancer treatment. In this method, radioactive microspheres are injected into the hepatic arterial bloodstream to target, irradiate, and kill cancer cells. Accurate and precise treatment planning can lead to more efficient and safer treatment by delivering a higher radiation dose to the tumor while minimizing the exposure of the surrounding liver parenchyma. Treatment planning primarily relies on the estimated radiation dose delivered to tissue. However, current methods used to estimate the dose are based on simplified assumptions that make the dosimetry results unreliable. In this work, we present a computational model to predict the radiation dose from the 90Y activity in different liver segments to provide a more realistic and personalized dosimetry. Computational fluid dynamics (CFD) simulations were performed in a 3D hepatic arterial tree model segmented from cone-beam CT angiographic data obtained from a patient with hepatocellular carcinoma (HCC). The microsphere trajectories were predicted from the velocity field. 90Y dose distribution was then calculated from the volumetric distribution of the microspheres. Two injection locations were considered for the microsphere administration, a lobar and a selective injection. Results showed that 22% and 82% of the microspheres were delivered to the tumor, after each injection, respectively, and the combination of both injections ultimately delivered 49% of the total administered 90Y microspheres to the tumor. Results also illustrated the nonhomogeneous distribution of microspheres between liver segments, indicating the importance of developing patient-specific dosimetry methods for effective radioembolization treatment.
Project description:BACKGROUND:Radioembolization, also known as transarterial radioembolization or selective internal radiation therapy with yttrium-90 (90Y) resin microspheres, is an established treatment modality for patients with primary and secondary liver tumors. However, large-scale prospective observational data on the application of this treatment in a real-life clinical setting is lacking. OBJECTIVE:The main objective is to collect data on the clinical application of radioembolization with 90Y resin microspheres to improve the understanding of the impact of this treatment modality in its routine practice setting. METHODS:Eligible patients are 18 years or older and receiving radioembolization for primary and secondary liver tumors as part of routine practice, as well as have signed informed consent. Data is collected