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1.
J Vasc Interv Radiol ; 34(7): 1214-1225, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36977431

RESUMO

Yttrium-90 transarterial radioembolization (TARE) has progressed from a salvage or palliative lobar or sequential bilobar regional liver therapy for patients with advanced disease to a versatile, potentially curative, and often highly selective local treatment for patients across Barcelona Clinic Liver Cancer stages. With this shift, radiation dosimetry has evolved to become more tailored to patients and target lesion(s), with treatment dose and distributions adapted for specific clinical goals (ie, palliation, bridging or downstaging to liver transplantation, converting to surgical resection candidacy, or ablative/curative intent). Data have confirmed that "personalizing" dosimetry yields real-world improvements in tumor response and overall survival while maintaining a favorable adverse event profile. In this review, imaging techniques used before, during, and after TARE have been reviewed. Historical algorithms and contemporary image-based dosimetry methods have been reviewed and compared. Finally, recent and upcoming developments in TARE methodologies and tools have been discussed.


Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Radiometria
2.
J Vasc Interv Radiol ; 34(3): 362-368, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36526074

RESUMO

PURPOSE: To evaluate the safety and efficacy of yttrium-90 (90Y) radiation segmentectomy (RS) in the treatment of oligometastatic secondary hepatic malignancies. MATERIALS AND METHODS: This 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. RESULTS: Clinical 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). CONCLUSIONS: 90Y RS displayed an excellent safety profile and was effective in achieving a high disease control rate in the treatment of oligometastatic secondary hepatic malignancies.


Assuntos
Neoplasias Hepáticas , Pneumonectomia , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Hepáticas/patologia , Radioisótopos de Ítrio/efeitos adversos
3.
J Vasc Interv Radiol ; 34(6): 968-975, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36791957

RESUMO

PURPOSE: To 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 METHODS: An 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. RESULTS: Seventy-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. CONCLUSIONS: In 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.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Estudos Retrospectivos , Radioisótopos de Ítrio/efeitos adversos
4.
J Vasc Interv Radiol ; 32(11): 1569-1574.e11, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34717835

RESUMO

The purpose of this study was to define the optimal infusion parameters and operator radiation exposure for yttrium-90 (90Y) radioembolization in the VX2 rabbit model of liver cancer. Forty-one rabbits with VX2 were treated with glass microspheres with vial sizes of 1, 3, and 5 GBq. The mean administered activity was 51.5 MBq (95% CI, 39.1-63.9). Delivery efficiency improved with 1 GBq versus with 3 GBq (residual 11.0% vs 46.4%, respectively; P = .0013) and improved with 1 GBq versus with 5 GBq (residual 11.0% vs 33.8%, respectively; P = .0060). The mean operator extremity exposure was 41.7 µSv/infusion. The optimal minimum infusion volume and rate was 49 mL and 21 mL/min, respectively. Fecal elimination occurred with microsphere uptake in the gallbladder at 1 and 2 weeks. 90Y radioembolization can be safely and efficiently performed in the VX2 rabbit model. Methodological considerations as a "how-to" for the setup of a preclinical 90Y laboratory are included to support future translational research.


Assuntos
Embolização Terapêutica , Neoplasias Hepáticas , Exposição à Radiação , Animais , Embolização Terapêutica/efeitos adversos , Neoplasias Hepáticas/radioterapia , Microesferas , Coelhos , Radioisótopos de Ítrio/efeitos adversos
5.
J Vasc Interv Radiol ; 32(1): 23-32.e1, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33189539

RESUMO

PURPOSE: To 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 METHODS: Hepatic 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. RESULTS: The 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. CONCLUSIONS: 90Y PET/CT estimates were strongly correlated and had better agreement with reference measurements of tumor dosing than SM estimates.


Assuntos
Embolização Terapêutica , Neoplasias Hepáticas Experimentais/diagnóstico por imagem , Neoplasias Hepáticas Experimentais/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Doses de Radiação , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Animais , Feminino , Necrose , Valor Preditivo dos Testes , Coelhos , Interpretação de Imagem Radiográfica Assistida por Computador , Carga Tumoral
6.
J Vasc Interv Radiol ; 32(2): 211-219, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33349507

RESUMO

PURPOSE: To 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 METHODS: This 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. RESULTS: The 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. CONCLUSIONS: Segmental 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.


Assuntos
Carcinoma Hepatocelular/terapia , Embolização Terapêutica , Neoplasias Hepáticas/terapia , Derivação Portossistêmica Transjugular Intra-Hepática , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Bases de Dados Factuais , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática/efeitos adversos , Derivação Portossistêmica Transjugular Intra-Hepática/mortalidade , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos
7.
J Vasc Interv Radiol ; 32(8): 1103-1112.e12, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33839262

RESUMO

PURPOSE: To investigate the feasibility, safety, and absorbed-dose distribution of prostatic artery radioembolization (RE) in a canine model. MATERIALS AND METHODS: Fourteen male castrated beagles received dihydroandrosterone/estradiol to induce prostatic hyperplasia for the duration of the study. Each dog underwent fluoroscopic prostatic artery catheterization. Yttrium-90 (90Y) microspheres (TheraSphere; Boston Scientific, Marlborough, Massachusetts) were delivered to 1 prostatic hemigland (dose escalation from 60 to 200 Gy), with the contralateral side serving as a control. Assessments for adverse events were performed throughout the follow-up (Common Terminology Criteria for Adverse Events v5.0). Positron emission tomography/magnetic resonance (MR) imaging provided a confirmation after the delivery of absorbed-dose distribution. MR imaging was performed before and 3, 20, and 40 days after RE. Tissue harvest of the prostate, rectum, bladder, urethra, penis, and neurovascular bundles was performed 60 days after RE. RESULTS: All the animals successfully underwent RE. Positron emission tomography/MR imaging demonstrated localization to and good coverage of only the treated hemigland. No adverse events occurred. The MR imaging showed a significant dose-dependent decrease in the treated hemigland size at 40 days (25%-60%, P < .001). No extraprostatic radiographic changes were observed. Necropsy demonstrated no gross rectal, urethral, penile, or bladder changes. Histology revealed RE-induced changes in the treated prostatic tissues of the highest dose group, with gland atrophy and focal necrosis. No extraprostatic RE-related histologic findings were observed. CONCLUSIONS: Prostate 90Y RE is safe and feasible in a canine model and leads to focal dose-dependent changes in the gland without inducing unwanted extraprostatic effects. These results suggest that an investigation of nonoperative prostate cancer is warranted.


Assuntos
Braquiterapia , Embolização Terapêutica , Neoplasias da Próstata , Animais , Cães , Humanos , Masculino , Próstata , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/radioterapia , Radioisótopos de Ítrio
8.
Radiographics ; 41(3): 909-928, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33939544

RESUMO

The renal arteries (RAs) are important vessels that usually arise from the abdominal aorta and supply the kidneys; thus, these arteries play a vital role in physiologic functions such as hemofiltration and blood pressure regulation. An understanding of the basis for embryologic development and the frequently variable anatomy of the RAs is necessary to fully appreciate the range of diseases and the implications for procedural planning. Hemorrhage from an RA is relatively common and is typically traumatic or spontaneous, with the latter form often seen in association with underlying tumors or arteriopathy. Accurate diagnostic evaluation of RA disease due to conditions such as atherosclerosis, fibromuscular dysplasia, vasculitis, aneurysm, arteriovenous shunt, embolic disease, and dissection is dependent on the use of multimodality imaging and is essential for selecting appropriate clinical management, with endovascular therapy having a key role in treatment. Surgical considerations include extra-anatomic renal bypass, which remains an important treatment option even in this era of endovascular therapy, and RA embolization as an adjunct to tumor surgery. A novel area of research interest is the potential role of RA denervation in the management of refractory hypertension. ©RSNA, 2021.


Assuntos
Fístula Arteriovenosa , Procedimentos Endovasculares , Aorta Abdominal , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/terapia , Humanos , Rim/diagnóstico por imagem , Artéria Renal/diagnóstico por imagem
9.
Radiology ; 287(1): 137-145, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29232185

RESUMO

Purpose To test the hypothesis that biomarkers of fluorine 18 (18F) fluorodeoxyglucose (FDG) positron emission tomography (PET) can be used for the early detection of therapeutic response to irreversible electroporation (IRE) of liver tumor in a rodent liver tumor model. Materials and Methods The institutional animal care and use committee approved this study. Rats were inoculated with McA-RH7777 liver tumor cells in the left median and left lateral lobes. Tumors were allowed to grow for 7 days to reach a size typically at least 5 mm in longest diameter, as verified with magnetic resonance (MR) imaging. IRE electrodes were inserted, and eight 100-µsec, 2000-V pulses were applied to ablate the tumor tissue in the left median lobe. Tumor in the left lateral lobe served as a control in each animal. PET/computed tomography (CT) and MR imaging measurements were performed at baseline and 3 days after IRE for each animal. Additional MR imaging measurements were obtained 14 days after IRE. After 14-day follow-up MR imaging, rats were euthanized and tumors harvested for hematoxylin-eosin, CD34, and caspase-3 staining. Change in the maximum standardized uptake value (ΔSUVmax) was calculated 3 days after IRE. The maximum lesion diameter change (ΔDmax) was measured 14 days after IRE by using axial T2-weighted imaging. ΔSUVmax and ΔDmax were compared. The apoptosis index was calculated by using caspase-3-stained slices of apoptotic tumor cells. Pearson correlation coefficients were calculated to assess the relationship between ΔSUVmax at 3 days and ΔDmax (or apoptosis index) at 14 days after IRE treatment. Results ΔSUVmax, ΔDmax, and apoptosis index significantly differed between treated and untreated tumors (P < .001 for all). In treated tumors, there was a strong correlation between ΔSUVmax 3 days after IRE and ΔDmax 14 days after IRE (R = 0.66, P = .01) and between ΔSUVmax 3 days after IRE and apoptosis index 14 days after IRE (R = 0.57, P = .04). Conclusion 18F-FDG PET imaging biomarkers can be used for the early detection of therapeutic response to IRE treatment of liver tumors in a rodent model. © RSNA, 2017.


Assuntos
Eletroporação/métodos , Fluordesoxiglucose F18 , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/terapia , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Animais , Biomarcadores/metabolismo , Modelos Animais de Doenças , Fígado/diagnóstico por imagem , Fígado/metabolismo , Neoplasias Hepáticas/diagnóstico por imagem , Ratos , Resultado do Tratamento
11.
Gastroenterology ; 151(6): 1155-1163.e2, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27575820

RESUMO

BACKGROUND & AIMS: Conventional transarterial chemoembolization (cTACE) is used to treat patients with hepatocellular carcinoma (HCC). Radioembolization is a minimally invasive procedure that involves implantation of radioactive micron-sized particles loaded with yttrium-90 (Y90) inside the blood vessels that supply a tumor. We performed a randomized, phase 2 study to compare the effects of cTACE and Y90 radioembolization in patients with HCC. METHODS: From October 2009 through October 2015, we reviewed patients with HCC of all Barcelona Clinic Liver Cancer (BCLC) stages for eligibility. Of these, 179 patients with BCLC stages A or B met our enrollment criteria and were candidates for cTACE or Y90 therapy. Patients were assigned randomly to groups that received Y90 therapy (n = 24; 50% Child-Pugh A) or cTACE (n = 21; 71% Child-Pugh A). The primary outcome was time to progression (TTP), evaluated by intention-to-treat analysis. Secondary outcomes included safety, rate of response (based on tumor size and necrosis criteria), and Kaplan-Meier survival time. We performed inverse probability of censoring weighting and competing risk analyses. RESULTS: Patients in the Y90 radioembolization group had significant longer median TTP (>26 mo) than patients in the cTACE group (6.8 mo; P = .0012) (hazard ratio, 0.122; 95% confidence interval [CI], 0.027-0.557; P = .007). This was confirmed by competing risk and inverse probability of censoring weighting analyses accounting for transplantation or death. A significantly greater proportion of patients in the cTACE group developed diarrhea (21%) than in the Y90 group (0%; P = .031) or hypoalbuminemia (58% in the cTACE group vs 4% in the Y90 group; P < .001). Similar proportions of patients in each group had a response to therapy, marked by necrosis (74% in the cTACE group vs 87% in the Y90 group) (P = .433). The median survival time, censored to liver transplantation, was 17.7 months for the cTACE group (95% CI, 8.3-not calculable) vs 18.6 months for the Y90 group (95% CI, 7.4-32.5) (P = .99). CONCLUSIONS: In a randomized phase 2 study of patients with HCC of BCLC stages A or B, we found Y90 radioembolization to provide significantly longer TTP than cTACE. Y90 radioembolization provides better tumor control and could reduce drop-out from transplant waitlists. ClinicalTrials.gov no. NCT00956930.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Radioisótopos de Ítrio/uso terapêutico , Idoso , Antineoplásicos/uso terapêutico , Quimioembolização Terapêutica/efeitos adversos , Diarreia/etiologia , Progressão da Doença , Intervalo Livre de Doença , Óleo Etiodado/uso terapêutico , Feminino , Humanos , Hipoalbuminemia/etiologia , Análise de Intenção de Tratamento , Transplante de Fígado , Masculino , Pessoa de Meia-Idade , Necrose , Estadiamento de Neoplasias , Estudos Prospectivos , Taxa de Sobrevida , Radioisótopos de Ítrio/efeitos adversos
12.
Radiology ; 278(2): 405-12, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26313619

RESUMO

PURPOSE: To investigate the qualitative and quantitative impacts of labeling yttrium microspheres with increasing amounts of superparamagnetic iron oxide (SPIO) material for magnetic resonance (MR) imaging in phantom and rodent models. MATERIALS AND METHODS: Animal model studies were approved by the institutional Animal Care and Use Committee. The r2* relaxivity for each of four microsphere SPIO compositions was determined from 32 phantoms constructed with agarose gel and in eight concentrations from each of the four compositions. Intrahepatic transcatheter infusion procedures were performed in rats by using each of the four compositions before MR imaging to visualize distributions within the liver. For quantitative studies, doses of 5, 10, 15, or 20 mg 2% SPIO-labeled yttrium microspheres were infused into 24 rats (six rats per group). MR imaging R2* measurements were used to quantify the dose delivered to each liver. Pearson correlation, analysis of variance, and intraclass correlation analyses were performed to compare MR imaging measurements in phantoms and animal models. RESULTS: Increased r2* relaxivity was observed with incremental increases of SPIO microsphere content. R2* measurements of the 2% SPIO-labeled yttrium microsphere concentration were well correlated with known phantom concentrations (R(2) = 1.00, P < .001) over a broader linear range than observed for the other three compositions. Microspheres were heterogeneously distributed within each liver; increasing microsphere SPIO content produced marked signal voids. R2*-based measurements of 2% SPIO-labeled yttrium microsphere delivery were well correlated with infused dose (intraclass correlation coefficient, 0.98; P < .001). CONCLUSION: MR imaging R2* measurements of yttrium microspheres labeled with 2% SPIO can quantitatively depict in vivo intrahepatic biodistribution in a rat model.


Assuntos
Dextranos/farmacocinética , Fígado/metabolismo , Imageamento por Ressonância Magnética/métodos , Ítrio/farmacocinética , Animais , Meios de Contraste/farmacocinética , Processamento de Imagem Assistida por Computador , Nanopartículas de Magnetita , Masculino , Microesferas , Modelos Animais , Imagens de Fantasmas , Ratos , Ratos Sprague-Dawley , Técnicas de Imagem de Sincronização Respiratória
13.
Radiology ; 274(1): 192-200, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25222066

RESUMO

PURPOSE: To test the following hypotheses in a murine model of pancreatic cancer: (a) Vaccination with antigen-loaded iron-labeled dendritic cells reduces T2-weighted signal intensity at magnetic resonance (MR) imaging within peripheral draining lymph nodes ( LN lymph node s) and (b) such signal intensity reductions are associated with tumor size changes after dendritic cell vaccination. MATERIALS AND METHODS: The institutional animal care and use committee approved this study. Panc02 cells were implanted into the flanks of 27 C57BL/6 mice bilaterally. After tumors reached 10 mm, cell viability was evaluated, and iron-labeled dendritic cell vaccines were injected into the left hind footpad. The mice were randomly separated into the following three groups (n = 9 in each): Group 1 was injected with 1 million iron-labeled dendritic cells; group 2, with 2 million cells; and control mice, with 200 mL of phosphate-buffered saline. T1- and T2-weighted MR imaging of labeled dendritic cell migration to draining LN lymph node s was performed before cell injection and 6 and 24 hours after injection. The signal-to-noise ratio ( SNR signal-to-noise ratio ) of the draining LN lymph node s was measured. One-way analysis of variance ( ANOVA analysis of variance ) was used to compare Prussian blue-positive dendritic cell measurements in LN lymph node s. Repeated-measures ANOVA analysis of variance was used to compare in vivo T2-weighted SNR signal-to-noise ratio LN lymph node measurements between groups over the observation time points. RESULTS: Trypan blue assays showed no significant difference in mean viability indexes (unlabeled vs labeled dendritic cells, 4.32% ± 0.69 [standard deviation] vs 4.83% ± 0.76; P = .385). Thirty-five days after injection, the mean left and right flank tumor sizes, respectively, were 112.7 mm(2) ± 16.4 and 109 mm(2) ± 24.3 for the 1-million dendritic cell group, 92.2 mm(2) ± 9.9 and 90.4 mm(2) ± 12.8 for the 2-million dendritic cell group, and 193.7 mm(2) ± 20.9 and 189.4 mm(2) ± 17.8 for the control group (P = .0001 for control group vs 1-million cell group; P = .00007 for control group vs 2-million cell group). There was a correlation between postinjection T2-weighted SNR signal-to-noise ratio decreases in the left popliteal LN lymph node 24 hours after injection and size changes at follow-up for tumors in both flanks (R = 0.81 and R = 0.76 for left and right tumors, respectively). CONCLUSION: MR imaging approaches can be used for quantitative measurement of accumulated iron-labeled dendritic cell-based vaccines in draining LN lymph node s. The amount of dendritic cell-based vaccine in draining LN lymph node s correlates well with observed protective effects.


Assuntos
Adenocarcinoma/imunologia , Adenocarcinoma/patologia , Antígenos/imunologia , Movimento Celular , Células Dendríticas/imunologia , Imageamento por Ressonância Magnética/métodos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/patologia , Imunidade Adaptativa , Animais , Linhagem Celular Tumoral , Dextranos/farmacologia , Modelos Animais de Doenças , Processamento de Imagem Assistida por Computador , Nanopartículas de Magnetita , Camundongos , Microscopia de Fluorescência , Vacinação
15.
J Vasc Interv Radiol ; 25(3): 397-404, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24315666

RESUMO

PURPOSE: To test whether iron oxide (IO)-containing yttrium aluminosilicate (YAS) microparticles (MPs) can generate localized therapeutic hyperthermia (≥ 43°C) when injected intratumorally in an animal model of liver cancer and whether MP distributions could be visualized with magnetic resonance (MR) imaging. MATERIALS AND METHODS: Twenty-one Sprague-Dawley rats implanted with N1-S1 liver tumors were assigned to alternating magnetic field (AMF) exposure following intratumoral injection with IO-YAS MPs (n = 7), sham surgery (n = 7), or baseline iron quantification (n = 7). Three fiberoptic probes allowed spatial and temporal monitoring of temperatures during 24 minutes of AMF exposure. T2-weighted turbo spin-echo MR imaging was performed within 1 hour after the procedure to detect signal voids caused by IO-YAS deposition. Hematoxylin and eosin-stained pathologic slides were also obtained, and the presence of IO-YAS was evaluated with inductively coupled plasma optical emission spectroscopy. RESULTS: Following AMF exposure, intratumoral temperatures after IO-YAS MP injection achieved therapeutic hyperthermia whereas those after sham surgery did not (46.6°C ± 1.3 vs 36.8°C ± 0.4; P < .0001). Within the treated group, the normal hepatic parenchyma (NHP) and rectal temperatures were 37.4°C ± 0.9 and 36.5°C ± 1.0 (P = .0809) at the conclusion of AMF exposure, respectively. A T2-weighted signal void at the tumor site was observed in all seven treated animals, and intratumoral IO-YAS was visualized on subsequent histopathologic examination in each case. The mean ratio of tumor:NHP Fe concentrations attributable to IO-YAS MPs was 108:1. CONCLUSIONS: AMF exposure of intratumoral IO-YAS MPs generates localized therapeutic hyperthermia in an animal model of liver cancer. MR detectability and potential for combination brachytherapy warrants further investigation for thermoradiotherapy in liver cancer.


Assuntos
Compostos Férricos/uso terapêutico , Hipertermia Induzida/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Imagem por Ressonância Magnética Intervencionista/métodos , Ítrio/uso terapêutico , Animais , Braquiterapia/métodos , Linhagem Celular Tumoral , Terapia Combinada/métodos , Estudos de Viabilidade , Masculino , Microesferas , Radioterapia Guiada por Imagem/métodos , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Resultado do Tratamento
16.
J Vasc Interv Radiol ; 25(10): 1523-32, 1532.e1-2, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25156827

RESUMO

PURPOSE: To determine, in an open-label, retrospective report, the safety and effectiveness of locoregional therapy with yttrium-90 ((90)Y) radioembolization for patients with progressing breast cancer liver metastases (BCLMs) despite multi-agent chemotherapy. MATERIALS AND METHODS: Seventy-five patients with progressing BCLMs and stable extrahepatic disease were treated with radioembolization at a single institution. Retrospective review of a prospectively collected database was performed to evaluate clinical and biochemical toxicities, tumor response, overall survival (OS), and time to progression. Radiologic response assessments included Response Evaluation Criteria In Solid Tumors in primary index lesions and metabolic activity on positron emission tomography (PET). Univariate and multivariate analyses were performed. RESULTS: The mortality rate at 30 days was 4% (n = 3). Clinical toxicity and hyperbilirubinemia of grade 3 or worse occurred in 7.6% (n = 5) and 5.9% of patients (n = 4), respectively. Partial response (PR) was seen in 35.3% of patients (n = 24), stable disease (SD) in 63.2% (n = 43), and progressive disease in 1.5% (n = 1). PET imaging was available in 25 patients, and 21 (84%) had a complete response, PR, or SD. The median OS was 6.6 months (95% confidence interval [CI], 5.0-9.2 mo). The hazard ratio (HR) for OS on multivariate analysis was 0.39 (95% CI, 0.23-0.66) for tumor burden less than 25% compared with greater burden. Elevated bilirubin levels were shown to reduce OS. The HR for hepatic progression was 0.22 (95% CI, 0.05-0.98) for solitary versus multifocal disease. CONCLUSIONS: Locoregional therapy with (90)Y radioembolization is safe and stops or delays the progression of targeted chemorefractory BCLMs. Adverse prognosticators were identified.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/mortalidade , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Radioisótopos de Ítrio/efeitos adversos
17.
Cancers (Basel) ; 16(4)2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38398226

RESUMO

INTRODUCTION: Image-guided renal mass biopsy is gaining increased diagnostic acceptance, but there are limited data concerning the safety and diagnostic yield of biopsy for small renal masses (≤4 cm). This study evaluated the safety, diagnostic yield, and management after image-guided percutaneous biopsy for small renal masses. METHODS: A retrospective IRB-approved study was conducted on patients who underwent renal mass biopsy for histopathologic diagnosis at a single center from 2015 to 2021. Patients with a prior history of malignancy or a renal mass >4 cm were excluded. Descriptive statistics were used to summarize patient demographics, tumor size, the imaging modality used for biopsy, procedure details, complications, pathological diagnosis, and post-biopsy management. A biopsy was considered successful when the specimen was sufficient for diagnosis without need for a repeat biopsy. Complications were graded according to the SIR classification of adverse events. A chi-squared test (significance level set at p ≤ 0.05) was used to compare the success rate of biopsies in different lesion size groups. RESULTS: A total of 167 patients met the inclusion criteria. The median age was 65 years (range: 26-87) and 51% were male. The median renal mass size was 2.6 cm (range: one-four). Ultrasound was solely employed in 60% of procedures, CT in 33%, a combination of US/CT in 6%, and MRI in one case. With on-site cytopathology, the median number of specimens obtained per procedure was four (range: one-nine). The overall complication rate was 5%. Grade A complications were seen in 4% (n = 7), consisting of perinephric hematoma (n = 6) and retroperitoneal hematoma (n = 1). There was one grade B complication (0.5%; pain) and one grade D complication (0.5%; pyelonephritis). There was no patient mortality within 30 days post-biopsy. Biopsy was successful in 88% of cases. A sub-group analysis showed a success rate of 85% in tumors <3 cm and 93% in tumors ≥3 cm (p = 0.01). Pathological diagnoses included renal cell carcinoma (65%), oncocytoma (18%), clear cell papillary renal cell tumors (9%), angiomyolipoma (4%), xanthogranulomatous pyelonephritis (1%), lymphoma (1%), high-grade papillary urothelial carcinoma (1%), and metanephric adenoma (1%), revealing benign diagnosis in 30% of cases. The most common treatment was surgery (40%), followed by percutaneous cryoablation (22%). In total, 37% of patients were managed conservatively, and one patient received chemotherapy. CONCLUSION: This study demonstrates the safety and diagnostic efficacy of image-guided biopsy of small renal masses. The diagnostic yield was significantly higher for masses 3-4 cm in size compared to those <3 cm. The biopsy results showed a high percentage of benign diagnoses and informed treatment decisions in most patients.

18.
Surg Endosc ; 27(2): 462-70, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22890478

RESUMO

BACKGROUND: The use of laparoscopy-assisted distal gastrectomy (LADG) in advanced gastric cancer (AGC) remains a controversial topic, mainly because of doubts about its oncologic validity. To date, literature on the prognosis for AGC after LADG is scarce. This study evaluated the procedure's long-term benefits compared with those of the conventional, open distal gastrectomy (ODG). METHODS: This study involved 201 patients, 66 of whom underwent LADG, with a mean follow-up period of 49.2 months, from January 1999 to March 2010. A clear set of criteria was used to select patients (including no evidence of lymph node metastasis) and surgeons (subject to their experience). Survival outcomes were assessed by Kaplan-Meier analysis and log-rank testing. The postoperative recovery and complications of the patients also were monitored. RESULTS: No significant difference was observed between LADG and ODG in terms of overall survival or disease-specific survival. The corresponding 5-year survival rates for individual tumor node metastasis stages also were comparable in each group. The number of lymph nodes harvested was similar in the two groups, although the operation time was significantly shorter for ODG. The postoperative hospital stay was shorter for LADG patients (average stay of 8.4 vs. 18.1 days in the ODG group; p < 0.001), and the postoperative complication rate was almost half that for ODG (13.6 vs. 25.0 %; p = 0.048). CONCLUSION: The combination of the long- and short-term data indicates that LADG should be considered as a feasible alternative to ODG for the treatment of AGC. Its widespread integration requires the accumulation of similar results across multiple centers worldwide.


Assuntos
Adenocarcinoma/cirurgia , Gastrectomia/métodos , Laparoscopia , Neoplasias Gástricas/cirurgia , Adenocarcinoma/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Fatores de Tempo
19.
Radiol Imaging Cancer ; 5(3): e220019, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37233207

RESUMO

Purpose To demonstrate the feasibility of using chemical shift fat-water MRI methods to visualize and measure intrahepatic delivery of ethiodized oil to liver tumors following conventional transarterial chemoembolization (cTACE). Materials and Methods Twenty-eight participants (mean age, 66 years ± 8 [SD]; 22 men) with hepatocellular carcinoma (HCC) treated with cTACE were evaluated with follow-up chemical shift MRI in this Health Insurance Portability and Accountability Act-compliant prospective, institutional review board-approved study. Uptake of ethiodized oil was evaluated at 1-month follow-up chemical shift MRI. Measurements of tumor size (MRI and CT), attenuation and enhancement (CT), fat content percentage, and tumor:normal ratio (MRI) were compared by lesion for responders versus nonresponders, as assessed with modified Response Evaluation Criteria in Solid Tumors and European Association for the Study of the Liver (EASL) criteria. Adverse events and overall survival by the Kaplan-Meier method were secondary end points. Results Focal tumor ethiodized oil retention was 46% (12 of 26 tumors) at 24 hours and 47% (18 of 38 tumors) at 1 month after cTACE. Tumor volume at CT did not differ between EASL-defined responders and nonresponders (P = .06). Tumor ethiodized oil volume measured with chemical shift MRI was statistically significantly higher for EASL-defined nonresponders (P = .02). Doxorubicin dosing (P = .53), presence of focal fat (P = .83), and a combined end point of focal fat and low doxorubicin dosing (P = .97) did not stratify overall survival after cTACE. Conclusion Chemical shift MRI allowed for assessment of tumor delivery of ethiodized oil out to 1 month after cTACE in participants with HCC and demonstrated tumor ethiodized oil volume as a potential tool for stratification of tumor response by EASL criteria. Keywords: MRI, Chemical Shift Imaging, CT, Hepatic Chemoembolization, Ethiodized Oil Clinicaltrials.gov registration no.: NCT02173119 Supplemental material is available for this article. © RSNA, 2023.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Masculino , Humanos , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Óleo Etiodado/efeitos adversos , Estudos de Viabilidade , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Doxorrubicina , Imageamento por Ressonância Magnética
20.
EJNMMI Phys ; 9(1): 21, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35312882

RESUMO

PURPOSE: To perform precision dosimetry in yttrium-90 radioembolization through CT imaging of radiopaque microspheres in a rabbit liver model and to compare extracted dose metrics to those produced from conventional PET-based dosimetry. MATERIALS AND METHODS: A CT calibration phantom was designed containing posts with nominal microsphere concentrations of 0.5 mg/mL, 5.0 mg/mL, and 25.0 mg/mL. The mean Hounsfield unit was extracted from the post volumes to generate a calibration curve to relate Hounsfield units to microsphere concentration. A nominal bolus of 40 mg of microspheres was administered to the livers of eight rabbits, followed by PET/CT imaging. A CT-based activity distribution was calculated through the application of the calibration curve to the CT liver volume. Post-treatment dosimetry was performed through the convolution of yttrium-90 dose-voxel kernels and the PET- and CT-based cumulated activity distributions. The mean dose to the liver in PET- and CT-based dose distributions was compared through linear regression, ANOVA, and Bland-Altman analysis. RESULTS: A linear least-squares fit to the average Hounsfield unit and microsphere concentration data from the calibration phantom confirmed a strong correlation (r2 > 0.999) with a slope of 14.13 HU/mg/mL. A poor correlation was found between the mean dose derived from CT and PET (r2 = 0.374), while the ANOVA analysis revealed statistically significant differences (p < 10-12) between the MIRD-derived mean dose and the PET- and CT-derived mean dose. Bland-Altman analysis predicted an offset of 15.0 Gy between the mean dose in CT and PET. The dose within the liver was shown to be more heterogeneous in CT than in PET with an average coefficient of variation equal to 1.99 and 1.02, respectively. CONCLUSION: The benefits of a CT-based approach to post-treatment dosimetry in yttrium-90 radioembolization include improved visualization of the dose distribution, reduced partial volume effects, a better representation of dose heterogeneity, and the mitigation of respiratory motion effects. Post-treatment CT imaging of radiopaque microspheres in yttrium-90 radioembolization provides the means to perform precision dosimetry and extract accurate dose metrics used to refine the understanding of the dose-response relationship, which could ultimately improve future patient outcomes.

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