A Simple Method for Estimating Dose Delivered to Hepatocellular Carcinoma after Yttrium-90 Glass-Based Radioembolization Therapy: Preliminary Results of a Proof of Concept Study

PurposeTo investigate a simple semiquantitative method to estimate yttrium-90 (⁹⁰Y) dose delivered with radioembolization to infiltrative hepatocellular carcinoma (HCC).Materials and MethodsIn a prospective study, patients with infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based ⁹⁰Y radioembolization including technetium-99m macroaggregated albumin (^99mTc-MAA) hepatopulmonary shunt study before therapy and bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) after ⁹⁰Y radioembolization. Baseline magnetic resonance imaging was coregistered with ^99mTc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity (⁹⁰Y radioactivity delivered to each cubic centimeter of tumor) was estimated based on a lobar infusion approach. Correlation between proportions of ^99mTc-MAA and ⁹⁰Y delivered to the tumor was investigated. Survival analysis was performed using Kaplan-Meier estimations.Results⁹⁰Y therapy was administered in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm³). Higher intratumoral ⁹⁰Y dose predicted prolonged survival, with 13.2-month median survival in patients with HCC and mean ⁹⁰Y dose of ≥ 100 Gy versus 4.6-month median survival for other patients (P < .001). Of administered ⁹⁰Y dose, 51.9% was delivered to the targeted tumors compared with 74.1% of ^99mTc-MAA with linear correlation between biodistribution of ^99mTc-MAA and ⁹⁰Y observed (Pearson r = 0.774, P < .001).ConclusionsThe findings in this study suggest that approximately 50% of administered ⁹⁰Y dose is taken up by targeted infiltrative HCC with PVT. Intratumoral ⁹⁰Y dose ≥ 100 Gy in unresectable infiltrative HCC via a lobar intraarterial approach is a positive prognostic factor for survival.     

Microsphere Localization and Dose Quantification Using Positron Emission Tomography/CT following Hepatic Intraarterial Radioembolization with Yttrium-90 in Patients with Advanced Hepatocellular Carcinoma

PurposeTo characterize the distribution of absorbed radiation dose after glass microsphere radioembolization for hepatocellular carcinoma (HCC) using yttrium-90 (⁹⁰Y) positron emission tomography/computed tomography (PET/CT).Materials and MethodsIn this retrospective study, 64 ⁹⁰Y PET/CT scans performed after treatment were evaluated following ⁹⁰Y glass-bead radioembolization in patients with advanced HCC. The intended dose to the target volume ranged from 83–129 Gy. Three-dimensional “dose maps” were created from reconstructed PET images using a voxel-based S-value transformation. Liver parenchyma and liver tumors were contoured on cross-sectional imaging and aligned with the created dose maps.ResultsThere were 113 tumors examined as part of 64 lobar treatments. The average tumor size was 4.8 cm ± 4.0 with an average tumor dose of 173 Gy ± 109. The average dose to the nontumor parenchyma within the target volume was 93.4 Gy ± 32.6, with on average 50% of the parenchymal voxels receiving > 79 Gy ± 23 and 10% receiving > 173 Gy ± 55. The average and median tumor-to-parenchymal weighted dose ratios were 2.2 and 1.9, respectively.ConclusionsUsing recommended dosimetry and administration techniques for lobar glass microsphere radioembolization, high doses to target tumors as well as background parenchyma were achieved on average with modest preferential uptake within tumors. There was wide variation in measured tumor and parenchymal doses after hepatic radioembolization for HCC, suggesting the need for continued development of patient-specific dosimetry.     

Quantitative Dosimetry for Yttrium-90 Radionuclide Therapy: Tumor Dose Predicts Fluorodeoxyglucose Positron Emission Tomography Response in Hepatic Metastatic Melanoma

PurposeTo assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases.Methods and MaterialsYttrium-90 (⁹⁰Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after ⁹⁰Y radioembolization was convolved with published ⁹⁰Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUV_max) and total lesion glycolysis (TLG).ResultsSeven patients with 30 tumors treated with ⁹⁰Y for hepatic metastatic melanoma with available ⁹⁰Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7–43.5 Gy), 28.6 Gy (13.8–65.6 Gy) and 36.6 Gy (20–124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2–7.9 months). Mean tumor dose (P = .03) and the percentage of tumor volume receiving ≥ 50 Gy (P < .01) significantly predicted for decrease in tumor SUV_max, whereas maximum tumor dose predicted for decrease in tumor TLG (P < .01).ConclusionsVolumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.     

Correlation and Agreement of Yttrium-90 Positron Emission Tomography/Computed Tomography with Ex Vivo Radioembolization Microsphere Deposition in the Rabbit VX2 Liver Tumor Model

PurposeTo demonstrate a stronger correlation and agreement of yttrium-90 (⁹⁰Y) positron emission tomography (PET)/computed tomography (CT) measurements with explant liver tumor dosing compared with the standard model (SM) for radioembolization.Materials and MethodsHepatic VX2 tumors were implanted into New Zealand white rabbits, with growth confirmed by 7 T magnetic resonance imaging. Seventeen VX2 rabbits provided 33 analyzed tumors. Treatment volumes were calculated from manually drawn volumes of interest (VOI) with three-dimensional surface renderings. Radioembolization was performed with glass ⁹⁰Y microspheres. PET/CT imaging was completed with scatter and attenuation correction. Three-dimensional ellipsoid VOI were drawn to encompass tumors on fused images. Tumors and livers were then explanted for inductively coupled plasma (ICP)-optical emission spectroscopy (OES) analysis of microsphere content. ⁹⁰Y PET/CT and SM measurements were compared with reference standard ICP-OES measurements of tumor dosing with Pearson correlation and Bland-Altman analyses for agreement testing with and without adjustment for tumor necrosis.ResultsThe median infused activity was 33.3 MBq (range, 5.9–152.9). Tumor dose was significantly correlated with ⁹⁰Y PET/CT measurements (r = 0.903, P < .001) and SM estimates (r = 0.607, P < .001). Bland-Altman analyses showed that the SM tended to underestimate the tumor dosing by a mean of ?8.5 Gy (CI, ?26.3–9.3), and the degree of underestimation increased to a mean of ?18.3 Gy (CI, ?38.5–1.9) after the adjustment for tumor necrosis.Conclusions⁹⁰Y PET/CT estimates were strongly correlated and had better agreement with reference measurements of tumor dosing than SM estimates.     

Clinical evaluation of the partition model for estimating radiation doses from yttrium-90 microspheres in the treatment of hepatic cancer

Radiation doses to the tumour and non-tumorous liver compartments from yttrium-90 microspheres in the treatment of hepatic cancer, as estimated by a partition model, have been verified by correlation with the actual doses measured with a beta probe at open surgery. The validity of the doses to the lungs, the tumour and non-tumorous liver compartment as estimated by the partition model was further evaluated in clinical settings. On the basis of the observation that one of three patients who received more than 30 Gy from a single treatment and one of two patients who received more than 50 Gy from multiple treatments developed radiation pneumonitis, it was deduced that an estimated lung dose <30 Gy from a single treatment and a cumulative lung dose <50 Gy from multiple treatments were probably the tolerance limits of the lungs. Three of five patients who received lung doses >30 Gy as estimated by the partition model and were predicted to develop radiation pneumonitis, did so despite the use of partial hepatic embolization to reduce the degree of lung shunting. Furthermore, a higher radiological response rate and prolonged survival were found in the group of patients who received higher tumour doses, as estimated by the partition model, than in the group with lower estimated tumour doses. Thus the radiation doses estimated by the partition model can be used to predict (a) complication rate, (b) response rate and (c) duration of survival in the same manner as the actual radiation doses measured with a beta probe at open surgery. The partition model has made selective internal radiation therapy using⁹⁰Y microspheres safe and repeatable without laparotomy.     

Praseodymium-142 microspheres for brachytherapy of nonresectable hepatic tumors

PurposeTo perform dosimetric study of ¹⁴²Pr microspheres for the use as a possible choice of radionuclide in microsphere brachytherapy of nonresectable hepatic tumor for faster dose delivery and facilitated dosimetry for quality assurance.Methods and MaterialsDose distributions of ¹⁴²Pr and ⁹⁰Y microspheres within hepatic tumors and blood vessels were calculated using MCNPX2.6 Monte Carlo code. The biological effective doses (BEDs) for ¹⁴²Pr and ⁹⁰Y microspheres were calculated and compared using the linear-quadratic model.ResultsDose distributions due to beta particles were similar for both ¹⁴²Pr and ⁹⁰Y. Total initial activity required to achieve the same total dose of 150 Gy at 2 cm from the center of the tumor was 0.662 GBq and 0.191 GBq for ¹⁴²Pr and ⁹⁰Y, respectively. For α/β ratio equal to 10 Gy, calculated BED values were 301.0 and 194.7 for ¹⁴²Pr and ⁹⁰Y, respectively, considering a total physical dose of 150 Gy.ConclusionsTotal dose delivery and dose distributions for both ¹⁴²Pr and ⁹⁰Y within tumors and blood vessels were obtained and compared. Shorter half-life of ¹⁴²Pr is an advantage, enabling a faster dose delivery. The higher BED found for ¹⁴²Pr implies potential improvement in the treatment effectiveness. ¹⁴²Pr showed to be an attractive option for applications in microsphere brachytherapy.     

Superselective Yttrium-90 Radioembolization for Hepatocellular Carcinoma Yields High Response Rates with Minimal Toxicity

PurposeTo assess the safety and efficacy of yttrium-90 (⁹⁰Y) radioembolization when performed in a superselective fashion for patients with unresectable hepatocellular carcinoma (HCC).Materials and MethodsThis retrospective study included 20 patients with unresectable HCC. Median Model for End-Stage Liver Disease score was 10.5 (range, 6–25), with 8 of 20 patients (40%) classified Child-Pugh class B and 1 of 20 patients (5%) classified class C cirrhosis. Segmental tumor-associated portal vein thrombus was present in 12 patients (60%), and a transjugular intrahepatic portosystemic shunt was present in 4 patients (20%). Median tumor diameter was 3.9 cm (range, 2.5–7.1 cm). All patients underwent superselective ⁹⁰Y radioembolization targeted to a single liver segment using glass microspheres.ResultsMedian dose to the treated segment was 254 Gy, and median dose to the tumor was 536 Gy. No grade 3–4 hepatotoxicity occurred. The most common clinical toxicities were fatigue (30%), abdominal pain (10%), and postembolization syndrome (10%). Follow-up imaging demonstrated complete European Association for the Study of the Liver response of the index tumor in 19 of 20 patients (95%) and stable disease in 1 of 20 patients (5%). In patients with complete response, local tumor recurrence rate was 5.3% (1 of 19 patients). Median time to progression was 319 days. Overall survival was 90% (18 of 20 patients) with a median follow-up period of 275 days (range, 32–677 d).ConclusionsWhen performed in a segmental fashion, ⁹⁰Y radioembolization demonstrates high response rates and low local tumor recurrence rates. Complete imaging response can be achieved in patients with locally aggressive disease. This study demonstrates no clinically significant hepatotoxicity, despite moderate liver dysfunction in many patients.     

Phase I/II 90Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) radioimmunotherapy dosimetry results in relapsed or refractory non-Hodgkin’s lymphoma

Dosimetry studies in patients with non-Hodgkin’s lymphoma were performed to estimate the radiation absorbed dose to normal organs and bone marrow from ⁹⁰Y-Zevalin (yttrium-90 ibritumomab tiuxetan, IDEC-Y2B8) treatment in this phase I/II, multicenter trial. The trial was designed to determine the dose of Rituximab (chimeric anti-CD20, Rituxan, IDEC-C2B8, MabThera), the unlabeled antibody given prior to the radioconjugate to clear peripheral blood B cells and optimize distribution, and to determine the maximum tolerated dose of ⁹⁰Y-Zevalin [7.4, 11, or 15 MBq/kg (0.2, 0.3, or 0.4 mCi/kg)]. Patients received ¹¹¹In-Zevalin (indium-111 ibritumomab tiuxetan, IDEC-In2B8 ) on day 0 followed by a therapeutic dose of ⁹⁰Y-Zevalin on day 7. Both doses were preceded by an infusion of the chimeric, unlabeled antibody Rituximab. Following administration of ¹¹¹In-Zevalin, serial anterior/posterior whole-body scans were acquired. Major-organ radioactivity versus time estimates were calculated using regions of interest. Residence times were computed and entered into the MIRDOSE3 computer software program to calculate estimated radiation absorbed dose to each organ. Initial analyses of estimated radiation absorbed dose were completed at the clinical site. An additional, centralized dosimetry analysis was performed subsequently to provide a consistent analysis of data collected from the seven clinical sites. In all patients with dosimetry data (n =56), normal organ and red marrow radiation absorbed doses were estimated to be well under the protocol-defined upper limit of 20 Gy and 3 Gy, respectively. Median estimated radiation absorbed dose was 3.4 Gy to liver (range 1.2–7.8 Gy), 2.6 Gy to lungs (range 0.72–4.4 Gy), and 0.38 Gy to kidneys (range 0.07–0.61 Gy). Median estimated tumor radiation absorbed dose was 17 Gy (range 5.8–67 Gy). No correlation was noted between hematologic toxicity and the following variables: red marrow radiation absorbed dose, blood T _1/2, blood AUC, plasma T _1/2, and plasma AUC. It is concluded that ⁹⁰Y-Zevalin administered at nonmyeloablative maximum tolerated doses results in acceptable radiation absorbed doses to normal organs. The only toxicity of note is hematologic and is not correlated to red marrow radiation absorbed dose estimates or T _1/2, reflecting that hematologic toxicity is dependent on bone marrow reserve in this heavily pretreated population. Received 24 January and in revised form 20 March 2000     

Outpatient Single-Session Yttrium-90 Glass Microsphere Radioembolization

PurposeTo investigate the feasibility of yttrium-90 (⁹⁰Y) glass microsphere radioembolization (including angiography, lung shunt assessment, and treatment) as a single-session, outpatient procedure.Materials and MethodsBetween January 2008 and June 2013, 14 patients underwent outpatient, single-session radioembolization with ⁹⁰Y glass microspheres. As part of the routine diagnostic work-up, all patients underwent either computed tomography (CT) or magnetic resonance imaging of the liver with three-dimensional analysis and had laboratory results forwarded to our center for confirmation of candidacy before treatment. On treatment day, all patients underwent planning mesenteric angiography with flat panel cone-beam CT imaging. Patients were administered 33–85 MBq of technetium-99m macroaggregated albumin (^99mTc-MAA) via a microcatheter positioned in a hepatic artery supplying the tumor of interest. Planar scintigraphy was initiated within 2 hours after the administration of ^99mTc-MAA and lung shunt fraction was determined. Final dosimetry calculations were performed while the patient was being transferred back from nuclear medicine to interventional radiology.ResultsAll patients successfully underwent planning angiography with administration of ^99mTc-MAA and ⁹⁰Y radioembolization as a single-session treatment. There were no reportable or recordable medical events; treatment was carried out to the desired dose in all cases. The mean total procedure time was 2.70 hours ± 0.72 (range, 1.63–3.97 h).ConclusionsThis study reports a novel proof of concept for performing radioembolization in a single-session setting. By using the described method, time between initial clinical assessments and radioembolization treatment is decreased, and costs are minimized.     

Accuracy and Safety of Scout Dose Resin Yttrium-90 Microspheres for Radioembolization Therapy Treatment Planning: A Prospective Single-Arm Clinical Trial

PurposeTo compare the accuracy and safety of 0.56 GBq resin yttrium-90 (⁹⁰Y) (scout⁹⁰Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic ⁹⁰Y (Rx⁹⁰Y) dose for patients with hepatocellular carcinoma (HCC).Materials and MethodsThis prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout⁹⁰Y. Rx⁹⁰Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout⁹⁰Y were compared with those by Rx⁹⁰Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout⁹⁰Y and MAA with that of Rx⁹⁰Y. The safety of scout⁹⁰Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout⁹⁰Y.ResultsThirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx⁹⁰Y. Scout⁹⁰Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx⁹⁰Y. Furthermore, the TNR and LSF of scout⁹⁰Y had a stronger agreement with those of Rx⁹⁰Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx⁹⁰Y, whereas scout⁹⁰Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout⁹⁰Y had a strong linear correlation with the TD and NTLD of Rx⁹⁰Y.ConclusionsCompared with MAA, scout⁹⁰Y is a more accurate surrogate for Rx⁹⁰Y biodistribution for nonsegmental therapies.     

Benign Biliary Stricture after Yttrium-90 Radioembolization for Hepatocellular Carcinoma

PurposeTo determine the frequency and possible causative factors of benign biliary stricture after radioembolization in patients with hepatocellular carcinoma (HCC).Materials and MethodsThis retrospective study comprised 232 patients with HCC who underwent yttrium-90 radioembolization between October 2015 and September 2019. Benign biliary stricture was defined as biliary ductal dilatation of segmental or lobar biliary ducts on follow-up images. Clinical and radiologic characteristics were compared using χ² test or independent t test.ResultsMean target perfused tissue dose was 224.6 Gy ± 106.8 (median, 205.7 Gy; range, 47.0–694.7 Gy). Of 232 patients, 15 (6.5%) had benign biliary stricture, which was detected from 3 weeks to 10.3 months (mean, 3.9 months; median, 3.2 months). Whereas 5 patients did not have any symptoms or signs associated with benign biliary stricture, 10 patients had cholangitis and/or laboratory abnormality requiring biliary drainage procedures and intravenous antibiotic therapy. Selective radioembolization through a caudate artery was performed in 55 (23.7%) patients. The incidence of benign biliary stricture was 16.4% (9/55) and 3.4% (6/177) in patients with and without selective radioembolization through a caudate artery, respectively (P = .002).ConclusionsBenign biliary stricture following yttrium-90 radioembolization may be common among patients receiving selective treatment via a caudate artery.     

Yttrium-90 Activity Quantification in PET/CT–Guided Biopsy Specimens from Colorectal Hepatic Metastases Immediately after Transarterial Radioembolization Using Micro–CT and Autoradiography

PurposeTo evaluate the yttrium-90 (⁹⁰Y) activity distribution in biopsy tissue samples of the treated liver to quantify the dose with higher spatial resolution than positron emission tomography (PET) for accurate investigation of correlations with microscopic biological effects and to evaluate the radiation safety of this procedure.Materials and MethodsEighty-six core biopsy specimens were obtained from 18 colorectal liver metastases (CLMs) immediately after ⁹⁰Y transarterial radioembolization (TARE) with either resin or glass microspheres using real-time ⁹⁰Y PET/CT guidance in 17 patients. A high-resolution micro–computed tomography (micro-CT) scanner was used to image the microspheres in part of the specimens and allow quantification of ⁹⁰Y activity directly or by calibrating autoradiography (ARG) images. The mean doses to the specimens were derived from the measured specimens’ activity concentrations and from the PET/CT scan at the location of the biopsy needle tip for all cases. Staff exposures were monitored.ResultsThe mean measured ⁹⁰Y activity concentration in the CLM specimens at time of infusion was 2.4 ± 4.0 MBq/mL. The biopsies revealed higher activity heterogeneity than PET. Radiation exposure to the interventional radiologists during post-TARE biopsy procedures was minimal.ConclusionsCounting the microspheres and measuring the activity in biopsy specimens obtained after TARE are safe and feasible and can be used to determine the administered activity and its distribution in the treated and biopsied liver tissue with high spatial resolution. Complementing ⁹⁰Y PET/CT imaging with this approach promises to yield more accurate direct correlation of histopathological changes and absorbed dose in the examined specimens.     

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.     

CT-based image-guided brachytherapy in uterine cervical cancer: Effect of tumor dose and volume on local control

Background and PurposeTo determine the optimal primary tumor dose for cervical cancer treatment using computed tomography (CT)-based image-guided brachytherapy (IGBT).Materials and MethodsWe retrospectively reviewed 171 patients with cervical cancer who underwent both external beam radiation therapy (EBRT) and IGBT between May 2015 and December 2019. Majority of EBRT plan included central shielding technique. CT-based IGBT was performed weekly a median of three times. Magnetic resonance imaging preceded the first and third session of IGBT for target delineation.ResultsThe median age of the patients was 64 years (range: 30–91 years). The median follow-up time for living patients was 43 months (range: 6–76 months). The 3-year local control rates according to the International Federation of Gynecology and Obstetrics (FIGO, 2008) stages were 89%, 100%, 92%, 89%, 78%, and 100% for stages IB, IIA, IIB, IIIA, IIIB, and IVA, respectively. The median EBRT dose to the central pelvis and parametrium/pelvic wall was 41.4 Gy and 50.4 Gy, respectively. Patients who received a cumulative 2 Gy equivalent dose (EQD2) (α/β = 10 Gy) of high-risk clinical target volume (HR CTV) D90% ≥ 75 Gy achieved a long-term local control rate of 93%, compared with 80% in those who received <75 Gy (p = 0.02).ConclusionThis is one of the largest CT-based IGBT series examining the treatment of cervical cancer based on the tumor dose-volume relationship. An HR CTV D90% ≥75 Gy was significantly associated with favorable local control in this study.     

Prospective Comparison of Hydrogel-coated Microcoils versus Fibered Platinum Microcoils in the Prophylactic Embolization of the Gastroduodenal Artery before Yttrium-90 Radioembolization

PurposeTo prospectively assess the performance of hydrogel-coated versus fibered microcoils in the prophylactic occlusion of the gastroduodenal artery (GDA) before yttrium-90 (⁹⁰Y) radioembolization.Materials and MethodsA total of 43 patients were randomized to receive fibered microcoils (n = 15), detachable hydrogel-coated microcoils (n = 13), or pushable hydrogel-coated microcoils (n = 15). Numbers of coils used, duration, dose–area product (DAP), contrast agent load, and coil migration were assessed. At the time of yttrium-90 (⁹⁰Y) radioembolization, persistent GDA occlusion was analyzed.ResultsIn all patients, the embolized GDA was still completely occluded at the time of ⁹⁰Y radioembolization. Mean numbers of microcoils used per patient were 11.5 (fibered microcoils), 2.9 (detachable hydrocoils), and 5.5 (pushable hydrocoils), with all numbers significantly different (P<.0001). Mean DAPs were 16,283 mGy/cm²±16,545 (standard deviation) for fibered microcoils, 13,786 mGy/cm²±5,990 for detachable hydrocoils, and 35,757 mGy/cm²±74,493 for pushable hydrocoils (P = .87). Mean durations of GDA coil embolization were 20 minutes for fibered microcoils, 25 minutes for detachable hydrocoils, and 32 minutes for pushable hydrocoils (P = .0015). Mean contrast agent loads were 9 mL for fibered microcoils, 11 mL for pushable hydrocoils, and 7 mL for detachable hydrocoils (P = .13). One case of coil migration occurred with each type.ConclusionsHydrogel-coated and fibered microcoils are equally effective for prophylactic occlusion of the GDA before radioembolization. The number of coils used is higher with fibered microcoils compared with pushable and detachable hydrocoils, but the reduced number of hydrocoils comes at the cost of increased procedure duration.     

Tumor Targeting and Three-Dimensional Voxel-Based Dosimetry to Predict Tumor Response,Toxicity, and Survival after Yttrium-90 Resin Microsphere Radioembolization in Hepatocellular Carcinoma

Purpose

To identify predictive factors of tumor response, progression-free survival (PFS), overall survival (OS), and toxicity using three-dimensional (3D) voxel-based dosimetry in patients with intermediate and advanced stage hepatocellular carcinoma (HCC) treated by yttrium-90 (⁹⁰Y) resin microspheres radioembolization (RE).

Modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver Criteria Using Delayed-Phase Imaging at an Early Time Point Predict Survival in Patients with Unresectable Intrahepatic Cholangiocarcinoma following Yttrium-90 Radioembolization

PurposeTo investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 (⁹⁰Y) radioembolization therapy.Materials and MethodsIn an institutional review board–approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent ⁹⁰Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan–Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P < .05.ResultsMedian overall survival (OS) from the time of ⁹⁰Y therapy was 16.3 months (95% confidence interval, 7.2–25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P < .001). Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria (P = .005 and P = .001, respectively) at 3 months. RECIST was not found to correlate with survival at 1- or 3-month follow-up.ConclusionsModified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after ⁹⁰Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival.     

放射性125I粒子离体照射模型的建立和测量

目的建立放射性^125I粒子离体照射模型,研究模型中离体细胞照射平面的剂量和剂量分布。方法应用14颗粒子环形排布的照射模型,用临床上常用的6711型^125I粒子。实验前随机抽取20%的粒子校正,应用TLD元件对模型进行测量。先用37MBq的^125I粒子照射6d,测量细胞平面受照剂量并计算初始剂量率;然后用同样活度的^125I粒子照射10d后测量,与用公式计算的照射剂量值进行比较。结果TLD标定：测量读数和照射剂量拟合为线性关系。单颗粒子活度测量值与出厂标定值相差〈±5%。照射6d测量细胞平面累积剂量为1.58Gy,计算初始剂量率为0.273Gy/d;照射10d的测量值和理论计算值分别为2.43和2.57Gy,两者相差5.76%。根据对模型的测量和计算,可推导出在不同的初始剂量率下受照剂量和照射时间的关系。结论建立的放射性125I粒子离体照射模型简便实用,可用于放射生物学实验研究。受照剂量与照射时间关系的建立,为今后开展放射性125I粒子相对生物效应的研究和对肿瘤细胞作用机制的研究奠定基础。     

胶体32P-磷酸铬间质给药对犬累积损伤效应的研究

目的 探讨胶体³²P-磷酸铬(³²P-CP)在正常Beagle犬的肝叶或臀大肌行间质注射的安全性。方法 10只Beagle犬,随机分成间质给药不同剂量(185和370MBq)、不同部位(臀大肌和肝脏)及冷胶体对照5组(n＝2)。术后不同时间点称量体重,行血液生化学检查,ECT轫致辐射显像,组织形态学动态观察及连续测量体表、血液、尿液和粪便放射性计数率值。计量数据以均数±标准差(±s)表示,采用SPSS13.0软件进行统计分析。结果 给药后ECT示肝脏组全肝显影,放射性分布呈团块状不均匀,肌肉组局部放射性持续浓聚,肝脏未见显影。术后第4组犬体重进行性减少,45d时较术前减少2.7kg,余组体重增值均数依序为3.0、1.6、0.8和3.1kg。第4组血小板、红细胞术后有明显减少。分别于给药后23和45d死亡,死亡前谷草转氨酶和谷丙转氨酶均有急剧升高;其余组间血液和血生化学差异无统计学意义。术后体表分区测定以注射部位放射性计数率值为最高,其次为膀胱、脾。肝脏组血液峰时为5min,峰值分别为0.5×10⁷/min和1.0×10⁷/min;肌肉组持续在3×10⁵/min左右。组织学表现肌肉组和肝脏185MBq组4周内有充血水肿改变,8周后组织结构恢复正常;肝脏370MBq组4周内部分肝细胞坏死,6周时见大量肝细胞气球样变,充血水肿明显,肝小叶结构不清。尿液、粪便中放射性计数率肌肉组峰时均数分别为13和12d,峰值为(42.0±3.3)×10⁴/min和(29.6±4.5)×10⁴/min;肝脏组峰时为5和9d,峰值为(49.0±10.2)×10⁴/min和(28.5±7.1)×10⁴/min。至30d肌肉组从尿液和粪便中累积排泄率为36.58%和10.62%,肝脏组为23.48%和8.76%。吸收剂量肝脏组肝脏为(30.6±2.3)、(55.6±4.4)Gy;肌肉组肌肉注射部位为(53.4±3.1)、(98.1±3.3)Gy,肝脏为(2.3±1.3)、(6.5±1.2)Gy。结论 Beagle犬肝脏间质注射794.39MBq/m²,肝脏吸收剂量为56Gy时有较强肝毒性及全身毒副作用,是其致死剂量。肌肉给药463.98～772.93MBq/m²是安全剂量范围。³²P-CP间质给药是适用于治疗凡穿刺所能到达的乏血供及中等血供实体瘤的安全手段。