Transarterial Radioembolization (TARE) Agents beyond 90Y-Microspheres.
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ABSTRACT:
SUBMITTER: Bouvry C
PROVIDER: S-EPMC6330886 | biostudies-other | 2018
REPOSITORIES: biostudies-other
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Project description:Transarterial radioembolization (TARE) is an emerging treatment for patients with unresectable hepatocellular carcinoma (HCC). This study successfully developed radiometal-labeled chitosan microspheres (111In/177Lu-DTPA-CMS) with a diameter of 36.5 ± 5.3 μm for TARE. The radiochemical yields of 111In/177Lu-DTPA-CMS were greater than 90% with high radiochemical purities (>98%). Most of the 111In/177Lu-DTPA-CMS were retained in the hepatoma and liver at 1 h after intraarterial (i.a.) administration. Except for liver accumulation, radioactivity in each normal organ was less than 1% of the injected radioactivity (%IA) at 72 h after injection. At 10 days after injection of 177Lu-DTPA-CMS (18.6 ± 1.3 MBq), the size of the hepatoma was significantly reduced by around 81%, while that of the rats in the control group continued to grow. This study demonstrated the effectiveness of 177Lu-DTPA-CMS in the treatment of N1-S1 hepatoma. 111In/177Lu-DTPA-CMS have the potential to be a superior theranostic pair for the treatment of clinical hepatoma.
| S-EPMC8953182 | biostudies-literature
Project description:INTRODUCTION:Strong correlation has been demonstrated between tumor dose and response and between healthy liver dose and side effects. Individualized dosimetry is increasingly recommended in the current clinical routine. However, hepatic and tumor segmentations could be complex in some cases. The aim of this study is to assess the reproducibility of the tumoral and non-tumoral liver dosimetry in selective internal radiation therapy (SIRT). MATERIAL AND METHODS:Twenty-three patients with hepatocellular carcinoma (HCC) who underwent SIRT with glass microspheres were retrospectively included in the study. Tumor (TV) and total liver volumes (TLV), and mean absorbed doses in tumoral liver (TD) and non-tumoral liver (THLD) were determined on the 90Y PET/CT studies using Simplicit90YTM software, by three independent observers. Dosimetry datasets were obtained by a medical physicist helped by a nuclear medicine (NM) physician with 10 years of experience (A), by a NM physician with 4-year experience (B), and by a resident who first performed 10 dosimetry assessments as a training (C). Inter-observer agreement was evaluated using intra-class correlation coefficients (ICC), coefficients of variation (CV), Bland-Altman plots, and reproducibility coefficient (RDC). RESULTS:A strong agreement was observed between all three readers for estimating TLV (ICC 0.98) and THLD (ICC 0.97). Agreement was lower for TV delineation (ICC 0.94) and particularly for TD (ICC 0.73), especially for the highest values. Regarding TD, the CV (%) was 26.5, 26.9, and 20.2 between observers A and B, A and C, and B and C, respectively, and the RDC was 1.5. Regarding THLD, it was 8.5, 12.7, and 9.4, and the RDC was 1.3. CONCLUSION:Using a standardized methodology, and regardless of the different experiences of the observers, the estimation of THLD is highly reproducible. Although the reproducibility of the assessment of tumor irradiation is overall quite high, large variations may be observed in a limited number of patients.
| S-EPMC7218042 | biostudies-literature
Project description: Not available
| S-EPMC10102768 | biostudies-literature
Project description:Unresectable primary and secondary liver malignancies present a major problem in the treatment of solid tumors. Transarterial radioembolization (TARE) is an increasingly used technique for treating various types of malignant liver tumors. This approach is appealing, as the mechanism of action is independent from other loco-regional treatments and potentially complementary to systemic therapies. There are two commercially available products in use for TARE: (90)Y-resin and (90)Y-glass microspheres. Currently available data indicates TARE so be safe and effective in hepatocellular carcinoma (HCC) and metastatic liver disease. In HCC the results compare well with chemoembolization, while the role of TARE in combination with kinase inhibitors has yet to be established. Current data on TARE in metastatic liver disease is promising, but there is a strong need for prospective randomized trials comparing TARE and modern chemotherapeutic regimen to support the growing role of TARE in metastatic liver disease.
| S-EPMC4882402 | biostudies-literature
Project description:A selective intra-arterial liver injection using yttrium-90-loaded microspheres as sources for internal radiation therapy is a form of transarterial radioembolization (TARE). Current data from the literature suggest that TARE is effective in hepatocellular carcinoma (HCC) and is associated with a low rate of adverse events; however, they are all based on retrospective series or non-controlled prospective studies, since randomized controlled trials comparing the other liver-directed therapies for intermediate and locally advanced stages HCC are still ongoing. The available data show that TARE provides similar or even better survival rates. TARE is very well tolerated and has a low rate of complications; these complications do not result from the embolic effects but mainly from the unintended irradiation to non-target tissue, including the liver parenchyma. The complications can be further reduced by accurate patient selection and a strict pre-treatment evaluation, including dosimetry and assessment of the vascular anatomy. First-line TARE is best indicated for intermediate-stage patients (according to the Barcelona Clinic Liver Cancer [BCLC] staging classification) who are poor candidates for transarterial chemoembolization or patients having locally advanced disease with segmental or lobar branch portal vein thrombosis. Moreover, data are emerging regarding the use of TARE in patients classified slightly above the criteria for liver transplantation with the purpose of downstaging them. TARE can also be applied as a second-line treatment in patients progressing to transarterial chemoembolization or sorafenib; a large number of Phase II/III trials are in progress in order to evaluate the best association with systemic therapies. Given the complexity of a correct treatment algorithm for potential TARE candidates and the need for clinical guidance, a comprehensive review was carried out analyzing both the best selection criteria of patients who really benefit from TARE and the new advances of this therapy which add significant value to the therapeutic weaponry against HCC.
| S-EPMC4918277 | biostudies-literature
Project description:Transarterial radioembolization (TARE) effectively treats unresectable primary and metastatic liver tumors through intra-arterial injection of Yttrium-90 (90 Y) beta particle emitting microspheres which implant around the tumor. Current dosimetry models are highly simplistic and there is a large need for an image-based dosimetry post-TARE, which would improve treatment safety and efficacy. Current post-TARE imaging is 90 Y bremsstrahlung SPECT/CT and we study the use of these images for dosimetry. Retrospective image review of ten patients having a Philips HealthcareTM SPECT/CT following TARE SIR-Spheres® implantation. Emission series with attenuation correction were resampled to 3 mm resolution and used to create image-based dose distributions. Dose distributions and analysis were performed in MIM Software SurePlanTM utilizing SurePlanTM Local Deposition Method (LDM) and a dose convolution method (WFBH). We sought to implement a patient-specific background subtraction prior to dose calculation to make these noisy bremsstrahlung SPECT images suitable for post-TARE dosimetry. On average the percentage of mean background counts to maximum count in the image across all patients was 9.4 ± 4.9% (maximum = 7.6%, minimum = 2.3%). Absolute dose increased and profile line width decreased as background subtraction value increased. The average value of the LDM and WFBH dose methods was statistically the same. As background subtraction value increased, the DVH curves become unrealistic and distorted. Background subtraction on bremsstrahlung SPECT image has a large effect on post-TARE dosimetry. The background contour defined provides a systematic estimate to the activity background that accounts for the scanner and patient conditions at the time of the image study and is easily implemented using commercially available software. Using the mean count in the background contour as a subtraction across the entire image gave the most realistic dose distributions. This methodology is independent of microsphere and software manufacturer allowing for use with any available products or tools.
| S-EPMC8035553 | biostudies-literature
Project description:BackgroundUsing data collected in the prospective observational study CIRSE Registry for SIR-Spheres Therapy, the present study aimed at identifying predictors of adverse events (AEs) following transarterial radioembolization (TARE) with Yttrium-90 resin microspheres for liver tumours.MethodsWe analysed 1027 patients enrolled between January 2015 and December 2017 and followed up for 24 months. Four hundred and twenty-two patients with hepatocellular carcinoma (HCC), 120 with intrahepatic carcinoma (ICC), 237 with colorectal liver metastases and 248 with liver metastases from other primaries were included. Prognostic factors were calculated with a univariable analysis by using the overall AEs burden score (AEBS).ResultsAll-cause AEs were reported in 401/1027 (39.1%) patients, with AEs associated with TARE, such as abdominal pain (16.6%), fatigue (17%), and nausea (11.7%) reported most frequently. Grade 3 or higher AEs were reported in 92/1027 (9%) patients. Reports on grade ≥ 3 gastrointestinal ulcerations (0.4%), gastritis (0.3%), radiation cholecystitis (0.2%) or radioembolization-induced liver disease (0.5%) were uncommon. Univariable analysis showed that in HCC, AEBS increased for Eastern Cooperative Oncology Group (ECOG) 0 (p = 0.0045), 1 tumour nodule (0.0081), > 1 TARE treatment (p = 0.0224), no prophylactic embolization (p = 0.0211), partition model dosimetry (p = 0.0007) and unilobar treatment target (0.0032). For ICC, > 1 TARE treatment was associated with an increase in AEBS (p = 0.0224), and for colorectal liver metastases, ECOG 0 (p = 0.0188), > 2 prior systemic treatments (p = 0.0127), and 1 tumour nodule (p = 0.0155) were associated with an increased AEBS.ConclusionOur study confirms that TARE is a safe treatment with low toxicity and a minimal impact on quality of life.
| S-EPMC10322946 | biostudies-literature
Project description:Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare primary liver tumor that typically presents at an advanced stage in early adolescents and adults with no underlying liver disease. Surgical resection is the first-line treatment, and patients who are not surgical candidates face limited treatment options with poor long-term outcomes. Herein we report the first documented, technically successful treatment of FL-HCC with extrahepatic spread using transarterial radioembolization (TARE) in a 16-year-old male patient with surgically unresectable disease. Subsequent imaging revealed tumor necrosis and a 20% reduction in size, and the patient survived 20 months post-treatment, a marked improvement relative to historical data in the literature. Further research should examine the potential role of yttrium-90 TARE in the treatment of FL-HCC patients with metastatic disease.
| S-EPMC7566208 | biostudies-literature
Project description:Intrahepatic cholangiocarcinoma (ICC) is a rare primary hepatic malignancy. One of the treatment strategies which has shown some promise is transarterial radioembolization (TARE). However, data on dose thresholds, arguably the most important aspect of the procedure itself, is still limited. The study aims to evaluate the relationship between dose to tumor and radiologic response in intrahepatic cholangiocarcinoma patients undergoing transarterial radioembolization. Twenty-patients who underwent treatment for 26 tumors were retrospectively reviewed. Radiologic response at 3-month was evaluated and post yttrium-90 bremsstrahlung single photon emission computerized tomography computed tomography was evaluated to determine tumor dose. Other factors such as particle load and activity per particle were evaluated. The mean tumor dose for those with progressive disease or stable disease, partial response, and complete response (CR) by European Association for the Study of Liver (EASL) criteria for the glass cohort was 294±0, 465.4±292.4 and 951.8±666.5 Gy respectively (P=0.039). A receiver operating characteristic (ROC) curve analysis of tumor dose demonstrated an area under the curve (AUC) of 0.738 (P=0.038) with Youden-index analysis demonstrated a cutoff point of >541.7 Gy (sensitivity: 55.56%; specificity: 92.86%) for the glass cohort. Significantly longer survival was noted in those who achieved a CR [HR: 4.79 (95% CI: 1.41-16.25)] and those treated with glass as compared to resin [HR: 5.02 (95% CI: 1.23-20.55), P=0.025]. Of the 17 treatments in 13 patients which were done concomitantly with chemotherapy 7/17 (41.2%) required a delay in chemotherapy, however all patients reinitiated chemotherapy after a delay. There appears to be a relationship between tumor dose and radiologic response, with this study suggesting a target of ≥541.7 Gy being warranted in patients receiving treatment with glass microspheres.
| S-EPMC10643573 | biostudies-literature
Project description:PurposeTransarterial radioembolization (TARE) is a treatment for liver tumours based on injection of radioactive microspheres in the hepatic arterial system. It is crucial to achieve a maximum tumour dose for an optimal treatment response, while minimizing healthy liver dose to prevent toxicity. There is, however, no intraprocedural feedback on the dose distribution, as nuclear imaging can only be performed after treatment. As holmium-166 (166Ho) microspheres can be quantified with MRI, we investigate the feasibility and safety of performing 166Ho TARE within an MRI scanner and explore the potential of intraprocedural MRI-based dosimetry.MethodsSix patients were treated with 166Ho TARE in a hybrid operating room. Per injection position, a microcatheter was placed under angiography guidance, after which patients were transported to an adjacent 3-T MRI system. After MRI confirmation of unchanged catheter location, 166Ho microspheres were injected in four fractions, consisting of 10%, 30%, 30% and 30% of the planned activity, alternated with holmium-sensitive MRI acquisition to assess the microsphere distribution. After the procedures, MRI-based dose maps were calculated from each intraprocedural image series using a dedicated dosimetry software package for 166Ho TARE.ResultsAdministration of 166Ho microspheres within the MRI scanner was feasible in 9/11 (82%) injection positions. Intraprocedural holmium-sensitive MRI allowed for tumour dosimetry in 18/19 (95%) of treated tumours. Two CTCAE grade 3-4 toxicities were observed, and no adverse events were attributed to treatment in the MRI. Towards the last fraction, 4/18 tumours exhibited signs of saturation, while in 14/18 tumours, the microsphere uptake patterns did not deviate from the linear trend.ConclusionThis study demonstrated feasibility and preliminary safety of a first in-human application of TARE within a clinical MRI system. Intraprocedural MRI-based dosimetry enabled dynamic insight in the microsphere distribution during TARE. This proof of concept yields unique possibilities to better understand microsphere distribution in vivo and to potentially optimize treatment efficacy through treatment personalization.RegistrationClinicaltrials.gov, identifier NCT04269499, registered on February 13, 2020 (retrospectively registered).
| S-EPMC9606012 | biostudies-literature