Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Humanos , Radioisótopos de Ítrio/uso terapêutico , Compostos Radiofarmacêuticos/uso terapêutico , AlemanhaAssuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagem , Embolização Terapêutica/métodos , Radioisótopos de Ítrio/uso terapêuticoRESUMO
BACKGROUND/AIMS: Hepatocellular carcinoma is a major cause of mortality and morbidity in both cirrhotic and non-cirrhotic patients, and most patients are suitable for locoregional and/or systemic therapy at the time of diagnosis. In this study, we aimed to determine the efficacy and safety of transarterial radioembolization in elderly patients. MATERIALS AND METHODS: Patients diagnosed with hepatocellular carcinoma between 2013 and 2022 were screened retrospectively. The patients were divided into 2 groups: the elderly (age >70 years) and the young (age <70 years). Transarterial radioembolization response was evaluated according to the Response Evaluation Criteria in Solid Tumors. RESULTS: Ninety patients were included in the young group, and 56 patients were in the elderly group. It was observed that male dominance was less in the elderly group (P > .05). Hepatitis B was the most common cause in both groups. There were no significant differences between groups with regard to morphological features of tumors [tumor focality (single; 62.2% and 60.7%, respectively) and maximal tumor diameter (6.9 and 6.55 cm, respectively)], transarterial radioembolization responses (51.1% and 39.3%, respectively), survival (9 and 8.5 months), and both early and late side effects (P > .05). Age was not found to be an effective factor in transarterial radioembolization response (P > .05). CONCLUSION: No differences in the safety and efficacy of transarterial radioembolization were observed between the groups. In addition, it was observed that age was not a predictive factor for adverse events. In elderly patients in the frail group, it should be considered that age alone should not be seen as a limitation in the transarterial radioembolization decision.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/mortalidade , Masculino , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/mortalidade , Feminino , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Resultado do Tratamento , Embolização Terapêutica/métodos , Embolização Terapêutica/efeitos adversos , Fatores Etários , Idoso de 80 Anos ou mais , Radioisótopos de Ítrio/uso terapêutico , Radioisótopos de Ítrio/administração & dosagem , AdultoRESUMO
ABSTRACT: Metastatic insulinomas can cause recurrent hypoglycemia requiring continuous IV glucose infusion. Various medical and chemotherapeutic treatment options are used to reduce the patient's risk of death due to hypoglycemia. Treatment-resistant hepatic metastatic insulinomas may benefit clinically from 90Y transarterial radioembolization therapy. In this case, we present a case of liver metastatic insulinoma that achieved clinical improvement after 2 cycles of 90Y microspheres transarterial radioembolization, and the presence of active metastases was demonstrated with 68Ga-NODAGA-exendin-4 PET/CT imaging.
Assuntos
Embolização Terapêutica , Exenatida , Radioisótopos de Gálio , Hipoglicemia , Insulinoma , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Ítrio , Humanos , Insulinoma/diagnóstico por imagem , Radioisótopos de Ítrio/uso terapêutico , Compostos Heterocíclicos com 1 Anel/uso terapêutico , Acetatos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/radioterapia , Masculino , Metástase Neoplásica , Pessoa de Meia-IdadeRESUMO
Objective.Contrast-enhanced computed tomography (CECT) is commonly used in the pre-treatment evaluation of liver Y-90 radioembolization feasibility. CECT provides detailed imaging of the liver and surrounding structures, allowing healthcare providers to assess the size, location, and characteristics of liver tumors prior to the treatment. Here we propose a method for translating CECT images to an expected dose distribution for tumor(s) and normal liver tissue.Approach.A pre-procedure CECT is used to obtain an iodine arterial-phase distribution by subtracting the non-contrast CT from the late arterial phase. The liver segments surrounding the targeted tumor are selected using Couinaud's method. The resolution of the resulting images is then degraded to match the resolution of the positron emission tomography (PET) images, which can image the Y-90 activity distribution post-treatment. The resulting images are then used in the same way as PET images to compute doses using the local deposition method. CECT images from three patients were used to test this method retrospectively and were compared with Y-90 PET-based dose distributions through dose volume histograms.Main results.Results show a concordance between predicted and delivered Y-90 dose distributions with less than 10% difference in terms of mean dose, for doses greater than 10% of the 98th percentile (D2%).Significance.CECT-derived predictions of Y-90 radioembolization dose distributions seem promising as a supplementary tool for physicians when assessing treatment feasibility. This dosimetry prediction method could provide a more comprehensive pre-treatment evaluation-offering greater insights than a basic assessment of tumor opacification on CT images.
Assuntos
Embolização Terapêutica , Neoplasias Hepáticas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Radioisótopos de Ítrio/uso terapêutico , Doses de Radiação , Meios de Contraste , Fígado/diagnóstico por imagem , Fígado/efeitos da radiação , Dosagem Radioterapêutica , Tomografia por Emissão de Pósitrons , Processamento de Imagem Assistida por Computador/métodosRESUMO
Objective.To investigate different dosimetric aspects of90Y-IsoPet™ intratumoral therapy in canine soft tissue sarcomas, model the spatial spread of the gel post-injection, evaluate absorbed dose to clinical target volumes, and assess dose distributions and treatment efficacy.Approach.Six canine cases treated with90Y-IsoPet™ for soft tissue sarcoma at the Veterinary Health Center, University of Missouri are analyzed in this retrospective study. The dogs received intratumoral IsoPet™ injections, following a grid pattern to achieve a near-uniform dose distribution in the clinical target volume. Two dosimetry methods were performed retrospectively using the Monte Carlo toolkit OpenTOPAS: imaging-based dosimetry obtained from post-injection PET/CT scans, and stylized phantom-based dosimetry modeled from the planned injection points to the gross tumor volume. For the latter, a Gaussian parameter with variable sigma was introduced to reflect the spatial spread of IsoPet™. The two methods were compared using dose-volume histograms (DVHs) and dose homogeneity, allowing an approximation of the closest sigma for the spatial spread of the gel post-injection. In addition, we compared Monte Carlo-based dosimetry with voxel S-value (VSV)-based dosimetry to investigate the dosimetric differences.Main results.Imaging-based dosimetry showed differences between Monte Carlo and VSV calculations in tumor high-density areas with higher self-absorption. Stylized phantom-based dosimetry indicated a more homogeneous target dose with increasing sigma. The sigma approximation of the90Y-IsoPet™ post-injection gel spread resulted in a median sigma of approximately 0.44 mm across all cases to reproduce the dose heterogeneity observed in Monte Carlo calculations.Significance.The results indicate that dose modeling based on planned injection points can serve as a first-order approximation for the delivered dose in90Y-IsoPet™ therapy for canine soft tissue sarcomas. The dosimetry evaluation highlights the non-uniformity of absorbed doses despite the gel spread, emphasizing the importance of considering tumor dose heterogeneity in treatment evaluation. Our findings suggest that using Monte Carlo for dose calculation seems more suitable for this type of tumor where high-density areas might play an important role in dosimetry.
Assuntos
Método de Monte Carlo , Radiometria , Cães , Animais , Dosagem Radioterapêutica , Radioisótopos de Ítrio/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Imagens de Fantasmas , Sarcoma/radioterapia , Sarcoma/veterináriaRESUMO
Functional liver parenchyma can be damaged from treatment of liver malignancies with 90Y selective internal radiation therapy (SIRT). Evaluating functional parenchymal changes and developing an absorbed dose (AD)-toxicity model can assist the clinical management of patients receiving SIRT. We aimed to determine whether there is a correlation between 90Y PET AD voxel maps and spatial changes in the nontumoral liver (NTL) function derived from dynamic gadoxetic acid-enhanced MRI before and after SIRT. Methods: Dynamic gadoxetic acid-enhanced MRI scans were acquired before and after treatment for 11 patients undergoing 90Y SIRT. Gadoxetic acid uptake rate (k1) maps that directly quantify spatial liver parenchymal function were generated from MRI data. Voxel-based AD maps, derived from the 90Y PET/CT scans, were binned according to AD. Pre- and post-SIRT k1 maps were coregistered to the AD map. Absolute and percentage k1 loss in each bin was calculated as a measure of loss of liver function, and Spearman correlation coefficients between k1 loss and AD were evaluated for each patient. Average k1 loss over the patients was fit to a 3-parameter logistic function based on AD. Patients were further stratified into subgroups based on lesion type, baseline albumin-bilirubin scores and alanine transaminase levels, dose-volume effect, and number of SIRT treatments. Results: Significant positive correlations (ρ = 0.53-0.99, P < 0.001) between both absolute and percentage k1 loss and AD were observed in most patients (8/11). The average k1 loss over 9 patients also exhibited a significant strong correlation with AD (ρ ≥ 0.92, P < 0.001). The average percentage k1 loss of patients across AD bins was 28%, with a logistic function model demonstrating about a 25% k1 loss at about 100 Gy. Analysis between patient subgroups demonstrated that k1 loss was greater among patients with hepatocellular carcinoma, higher alanine transaminase levels, larger fractional volumes of NTL receiving an AD of 70 Gy or more, and sequential SIRT treatments. Conclusion: Novel application of multimodality imaging demonstrated a correlation between 90Y SIRT AD and spatial functional liver parenchymal degradation, indicating that a higher AD is associated with a larger loss of local hepatocyte function. With the developed response models, PET-derived AD maps can potentially be used prospectively to identify localized damage in liver and to enhance treatment strategies.
Assuntos
Fígado , Imageamento por Ressonância Magnética , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Ítrio , Humanos , Masculino , Feminino , Fígado/diagnóstico por imagem , Pessoa de Meia-Idade , Radioisótopos de Ítrio/uso terapêutico , Idoso , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Gadolínio DTPA , Testes de Função Hepática , Dosagem RadioterapêuticaRESUMO
BACKGROUND: Evaluating transarterial radioembolization (TARE) in patients with metastatic colorectal carcinoma of the liver who have progressed on first-line chemotherapy (EPOCH) demonstrated superior outcomes using yttrium-90 glass microspheres plus chemotherapy (TARE/Chemo) vs chemotherapy (Chemo) to treat colorectal liver metastases. Additional exploratory analyses were undertaken to assess the impact of TARE/Chemo on efficacy, safety, time to subsequent therapy, time to deterioration in quality of life (QoL), and identify criteria for improved patient selection. METHODS: Time to deterioration in QoL was analyzed for the primary study population. Subsequently, a post hoc analysis was undertaken to identify subgroups for which time to deterioration in QoL was improved with TARE/Chemo vs Chemo. Progression-free survival (PFS), hepatic (h)PFS, time to subsequent therapy, and safety outcomes were compared between treatments. RESULTS: The primary population showed no significant difference in time to deterioration in QoL between treatment arms; however, significance was seen in 2 identified subgroups, namely: Subgroup A (Nâ =â 303) which excluded patients with both Eastern Cooperative Oncology Group (ECOG) 1 and baseline CEAâ ≥â 35 ng/mL from both treatment arms; subgroup B (Nâ =â 168) additionally excluded patients with KRAS (Kirsten rat sarcoma) mutation. In subgroup A, TARE/Chemo patients (Nâ =â 143) demonstrated superior outcomes vs Chemo (Nâ =â 160): PFS (9.4 vs. 7.6 months, hazard ratio (HR): 0.64; 1-sided Pâ =â .0020), hPFS (10.8 vs. 7.6 months, HR: 0.53; 1-sided Pâ <â .0001), time to deterioration in QoL (5.7 vs. 3.9 months, HR: 0.65; 1-sided Pâ =â .0063), and time to subsequent therapy (21.2 vs. 10.5 months, HR: 0.52; 1-sided Pâ <â .0001). Subgroup B patients showed similar but larger significant differences between treatment arms. Median PFS, hPFS, and time to deterioration in QoL were numerically greater for TARE/Chemo in both subgroups vs the primary population, with the greatest magnitude of difference in subgroup B. Both subgroups exhibited higher percentage of CEA responders and improved ORR with TARE/Chemo vs chemo alone. Safety (reported as event rate/100 patient-years) was higher with Chemo in all populations. Additional efficacy analyses in the primary population are also reported. CONCLUSIONS: Careful patient selection, including consideration of the prognostic factors ECOG, baseline CEA, and KRAS status, sets outcome expectations in patients with colorectal liver metastases suitable for TARE/Chemo as second-line treatment (Trial Registry Number: NCT01483027).
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Qualidade de Vida , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/terapia , Radioisótopos de Ítrio/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Seleção de Pacientes , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , VidroRESUMO
Yttrium-90 (90Y) transarterial radioembolization can safely and effectively treat hepatocellular carcinoma (HCC). Clinical trials combining 90Y with immunotherapy are aimed at improving treatment response rates. The impact of transient 90Y-induced lymphopenia on T-cell homeostasis and functional dynamics is unknown. Paired blood specimens were collected prior to first-cycle 90Y and at imaging follow-up in patients with HCC Barcelona Clinic Liver Cancer stages A-B. Flow cytometry and T-cell receptor (TCR) sequencing were used to monitor changes in T-cell subsets and TCR repertoire following 90Y. Objective response (OR) rates were determined using modified RECIST and defined as either OR or nonobjective response. Time-to-progression (TTP) was defined as progression to Barcelona Clinic Liver Cancer stage C within 6 months following 90Y. 90Y induced shifts in both CD4+ (P = 0.049) and CD8+ (P < 0.001) toward an effector memory T-cell response independent of treatment response rate. Nonresponders to 90Y were characterized by a sustained elevation in both naïve CD4+ cells (P = 0.019) and programmed cell death protein 1 expression in CD8+ cells (P = 0.003). Paired analysis of the TCR repertoire revealed a variable induction of neoantigen clonotypes and expansion of existing clonotypes independent of 90Y response. In patients with an OR, changes in TCR clonality did not influence TTP. However, polyclonal profiles in patients without an OR were associated with shorter TTP (P = 0.005; HR, 10.8) and 75% disease progression rates 6 months following treatment. 90Y induces a population shift from central to effector memory accompanied by neoantigen T-cell responses independent of treatment response rate. Monoclonal shifts in the post-90Y T-cell repertoire had superior overall TTP and improved TTP in patients with a first-cycle nonobjective response. SIGNIFICANCE: 90Y can safely treat HCC; however, it causes transient lymphopenia. In this article, 90Y stimulates a peripheral effector memory response independent of initial treatment response. TCR sequencing revealed that polyclonal profiles in patients without an OR to treatment were associated with rapid progression rates 6 months after 90Y.
Assuntos
Carcinoma Hepatocelular , Imunoterapia , Neoplasias Hepáticas , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Masculino , Feminino , Radioisótopos de Ítrio/uso terapêutico , Pessoa de Meia-Idade , Imunoterapia/métodos , Idoso , Memória Imunológica , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/genética , Antígenos de Neoplasias/imunologia , Linfócitos T CD8-Positivos/imunologia , AdultoRESUMO
PURPOSE: Transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) is performed after a mapping angiogram involving infusion of radiolabeled macroaggregated albumin to assess for non-target embolization and pulmonary shunting. The purpose of this case series was to evaluate the safety and feasibility of single-session TARE without the initial procedure. MATERIALS AND METHODS: A single-institution case series of 16 consecutive procedures on 15 patients with 18 tumors who underwent an attempted single-session TARE procedures with glass microspheres are presented. A lung shunt fraction (LSF) of 5% was assumed for planning purposes. RESULTS: Sixty-seven percent (10/15) of patients were male with a median age of 72 years. Median tumor size was 2.5 cm (IQR 2.0-3.2 cm). Sixteen of the 18 targeted tumors were untreated prior to the single-session TARE. Rate of technical success was 88% (14/16). Two patients did not ultimately receive a single-session TARE due to intraprocedural findings. The mean administered activity was 2.0 GBq, and the mean MIRD dose was 464 Gy based on pre-treatment anatomic imaging and 800 Gy based on cone-beam CT. There were no cases of radiation pneumonitis. Mean post-procedural calculated lung dose was 4.9 Gy (range 3.1-9.3) based on SPECT. CONCLUSIONS: An initial experience with single-session TARE using Y-90 glass microspheres without pre-procedural mapping angiography and lung shunt estimation demonstrates that it is a feasible and safe treatment option for select patients with small (< 5 cm) HCC. LEVEL OF EVIDENCE IV: Level 4 case series.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Microesferas , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/terapia , Masculino , Idoso , Feminino , Embolização Terapêutica/métodos , Pessoa de Meia-Idade , Resultado do Tratamento , Radioisótopos de Ítrio/uso terapêutico , Estudos de Viabilidade , Idoso de 80 Anos ou mais , Angiografia , Compostos Radiofarmacêuticos , Estudos RetrospectivosRESUMO
In the1980s, radiolabeled cells helped understand the pathology of hemato-oncology. In the 1990s, preclinical trials evaluated radiolabeled immunotherapy with monoclonal antibodies (MoAbs) such as anti-CD20 agents labeled with Iodine-131 (Bexxar) or Yttrium-90 (Zevalin). Due to the safe and durable responses of radiolabeled MoAbs, the Food and Drug Administration approved these agents in the 2000s. Despite radioimmunotherapy's long journey, its application has recently decreased. This review will discuss the historical timeline of radioimmunotherapy, debate on advantages and difficulties, and explore trials. We will examine future directions of radioligand therapy in hemato-oncology, considering emerging molecules that may become the next theragnostic trend.
Assuntos
Linfoma , Radioimunoterapia , Compostos Radiofarmacêuticos , Humanos , Anticorpos Monoclonais/uso terapêutico , História do Século XX , História do Século XXI , Radioisótopos do Iodo/uso terapêutico , Linfoma/radioterapia , Linfoma/diagnóstico por imagem , Radioimunoterapia/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêuticoRESUMO
BACKGROUND: Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. METHODS: We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. RESULTS: One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). CONCLUSIONS: These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Estadiamento de Neoplasias , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Braquiterapia/métodos , Radioisótopos de Ítrio/uso terapêutico , Resultado do TratamentoRESUMO
The benefit of multicompartment dosimetry in the radioembolization of neuroendocrine neoplasms is not firmly established. We retrospectively assessed its potential with patient outcome. Methods: Forty-three patients were eligible. The association of mean absorbed dose (MAD) for tumors and treatment response was tested per lesion with a receiver operating characteristic curve analysis, and the association of MAD with progression-free survival (PFS) and overall survival was tested per patient using uni- and multivariate Cox regression analyses. Results: The area under the curve for treatment response based on MAD was 0.79 (cutoff, 196.6 Gy; P < 0.0001). For global PFS, grade (grade 2 vs. 1: hazard ratio [HR], 2.51; P = 0.042; grade 3 vs. 1: HR, 62.44; P < 0.001), tumor origin (HR, 6.58; P < 0.001), and MAD (HR, 0.998; P = 0.003) were significant. For overall survival, no prognostic parameters were significant. Conclusion: In line with prior publications, a MAD of more than 200 Gy seemed to favor treatment response. MAD was also associated with PFS and may be of interest for radioembolization planning for neuroendocrine neoplasm patients.
Assuntos
Relação Dose-Resposta à Radiação , Embolização Terapêutica , Neoplasias Hepáticas , Microesferas , Tumores Neuroendócrinos , Radioisótopos de Ítrio , Humanos , Tumores Neuroendócrinos/radioterapia , Tumores Neuroendócrinos/patologia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Masculino , Feminino , Radioisótopos de Ítrio/uso terapêutico , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Vidro/química , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Personalized dosimetry improves overall survival (OS) in patients with hepatocellular carcinoma (HCC) treated with glass 90 Y radioembolization. This study evaluated personalized tumor dose (TD) as a predictor of OS, progression-free survival (PFS), and local duration of response (DOR) in patients with surgically unresectable HCC treated with resin 90 Y radioembolization. PATIENTS AND METHODS: This prospective, single-center, single-arm clinical trial (NCT04172714) evaluated the efficacy of scout activity of resin 90 Y versus 99m Tc-MAA for treatment planning. A secondary aim of this study was to evaluate personalized dosimetry as a predictor of OS, PFS, and DOR. Partition dosimetry model was utilized for nonsegmental therapies with targeted TD >200 Gy and nontumoral liver dose <70 Gy. Single compartment dose of 200 Gy was used for segmentectomies. OS, PFS, and local DOR from 90 Y was estimated using Kaplan-Meier estimation with log-rank analysis used to determine predictors of prolonged survival. FINDINGS: Thirty patients with treatment-naive HCC and 33 tumors (19 segmental and 14 nonsegmental) were included. Overall, 18 patients underwent segmental Y90-RE and 12 underwent non-segmental/lobar therapies. The mean 90 Y TD was 493 Gy. The median follow-up since enrollment into the study was 37 months. The mean OS was 32.2 months for the entire cohort. A total of 5 patients underwent orthotopic liver transplantation post 90 Y and were excluded from further survival analysis. The mean OS for the remainder of the cohort was 30.1 months (median not reached). The mean TD >250 Gy resulted in prolonged mean OS and PFS. The median local DOR was 32.7 months with mean TD 330 Gy predicting prolonged DOR. INTERPRETATION: For patients with surgically unresectable HCC treated with resin 90 Y, there is mean TD threshold predicting prolonged OS, PFS, and local DOR. Therefore, there should be further emphasis on personalized dosimetry for optimization of patient outcomes.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Radioisótopos de Ítrio , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/cirurgia , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/radioterapia , Masculino , Radioisótopos de Ítrio/uso terapêutico , Feminino , Estudos Prospectivos , Pessoa de Meia-Idade , Idoso , Dosagem Radioterapêutica , Resultado do Tratamento , Adulto , Idoso de 80 Anos ou maisAssuntos
Embolização Terapêutica , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Radioisótopos de Ítrio , Humanos , Radioisótopos de Ítrio/uso terapêutico , Embolização Terapêutica/métodos , Medicina de Precisão/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Radiometria , Imagem Corporal TotalRESUMO
We report the results of a Phase I radiation dose escalation study using an yttrium-90 (90Y) labelled anti-CD66 monoclonal antibody given with standard conditioning regimen for patients receiving haematopoietic stem cell transplants for myeloid leukaemia or myeloma. The 90Y-labelled anti-CD66 was infused prior to standard conditioning. In total, 30 patients entered the trial and 29 received 90Y-labelled mAb, at infused radiation activity levels of 5, 10, 25, or 37.5 megaBequerel (MBq)/kg lean body weight. A prerequisite for receiving the 90Y-labelled mAb was favourable dosimetry determined by single-photon emission computerised tomography (SPECT) dosimetry following administration of indium-111 (111In) anti-CD66. Estimated absorbed radiation doses delivered to the red marrow demonstrated a linear relationship with the infused activity of 90Y-labelled mAb. At the highest activity level of 37.5 MBq/kg, mean estimated radiation doses for red marrow, liver, spleen, kidneys and lungs were 24.6 ± 5.6 Gy, 5.8 ± 2.7 Gy, 19.1 ± 8.0 Gy, 2.1 ± 1.1 and 2.2 ± 0.9, respectively. All patients engrafted, treatment-related mortality 1-year post-transplant was zero. Toxicities were no greater than those anticipated for similar conditioning regimens without targeted radiation. The ability to substantially intensify conditioning prior to haematopoietic stem cell transplantation without increasing toxicity warrants further testing to determine efficacy. clinicaltrials.gov identifier: NCT01521611.
Assuntos
Medula Óssea , Transplante de Células-Tronco Hematopoéticas , Radioisótopos de Ítrio , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Radioisótopos de Ítrio/uso terapêutico , Radioisótopos de Ítrio/farmacocinética , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Idoso , Medula Óssea/efeitos da radiação , Medula Óssea/metabolismo , Anticorpos Monoclonais/uso terapêutico , Condicionamento Pré-Transplante/métodos , Antígenos CD , Mieloma Múltiplo/terapia , Leucemia Mieloide/terapiaRESUMO
The dosimetry evaluation for the selective internal radiation therapy is currently performed assuming a uniform activity distribution, which is in contrast with literature findings. A 2D microscopic model of the perfused liver was developed to evaluate the effect of two different 90Y microspheres distributions: i) homogeneous partitioning with the microspheres equally distributed in the perfused liver, and ii) tumor-clustered partitioning where the microspheres distribution is inferred from the patient specific images. METHODS: Two subjects diagnosed with liver cancer were included in this study. For each subject, abdominal CT scans acquired prior to the SIRT and post-treatment 90Y positron emission tomography were considered. Two microspheres partitionings were simulated namely homogeneous and tumor-clustered partitioning. The homogeneous and tumor-clustered partitionings were derived starting from CT images. The microspheres radiation is simulated by means of Russell's law. RESULTS: In homogenous simulations, the dose delivery is uniform in the whole liver while in the tumor-clustered simulations a heterogeneous distribution of the delivered dose is visible with higher values in the tumor regions. In addition, in the tumor-clustered simulation, the delivered dose is higher in the viable tumor than in the necrotic tumor, for all patients. In the tumor-clustered case, the dose delivered in the non-tumoral tissue (NTT) was considerably lower than in the perfused liver. CONCLUSIONS: The model proposed here represents a proof-of-concept for personalized dosimetry assessment based on preoperative CT images.
Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Microesferas , Dosagem Radioterapêutica , Radioisótopos de Ítrio , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/diagnóstico por imagem , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Radioisótopos de Ítrio/uso terapêutico , Modelos Biológicos , Tomografia Computadorizada por Raios X , Doses de Radiação , MicroscopiaRESUMO
This study showcases a comprehensive treatment protocol for high-risk hepatocellular carcinoma (HCC) patients, focusing on the combined use of Y-90 transarterial radioembolization (TARE) and Programmed Cell Death-1 (PD-1) inhibitors as neoadjuvant therapy. Highlighted through a case report, it offers a step-by-step reference for similar therapeutic interventions. A retrospective analysis was conducted on a patient who underwent hepatectomy following Y-90 TARE and PD-1 inhibitor treatment. Key demographic and clinical details were recorded at admission to guide therapy selection. Y-90 TARE suitability and dosage calculation were based on Technetium-99m (Tc-99m) macroaggregated albumin (MAA) perfusion mapping tests. Lesion coverage by Y-90 microspheres was confirmed through single photon emission computed tomography/computed tomography (SPECT/CT) fusion imaging, and adverse reactions and follow-up outcomes were meticulously documented. The patient, with a 7.2 cm HCC in the right hepatic lobe (T1bN0M0, BCLC A, CNLC Ib) and an initial alpha-fetoprotein (AFP) level of 66,840 ng/mL, opted for Y-90 TARE due to high recurrence risk and initial surgery refusal. The therapy's parameters, including the lung shunting fraction (LSF) and non-tumor ratio (TNR), were within therapeutic limits. A total of 1.36 GBq Y-90 was administered. At 1 month post-therapy, the tumor shrank to 6 cm with partial necrosis, and AFP levels dropped to 21,155 ng/mL, remaining stable for 3 months. After 3 months, PD-1 inhibitor treatment led to further tumor reduction to 4 cm and AFP decrease to 1.84 ng/mL. The patient then underwent hepatectomy; histopathology confirmed complete tumor necrosis. At 12 months post-surgery, no tumor recurrence or metastasis was observed in follow-up sessions. This protocol demonstrates the effective combination of Y-90 TARE and PD-1 inhibitor as a bridging strategy to surgery for HCC patients at high recurrence risk, providing a practical guide for implementing this approach.
Assuntos
Carcinoma Hepatocelular , Embolização Terapêutica , Neoplasias Hepáticas , Terapia Neoadjuvante , Radioisótopos de Ítrio , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Terapia Neoadjuvante/métodos , Embolização Terapêutica/métodos , Radioisótopos de Ítrio/uso terapêutico , Masculino , Estudos Retrospectivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Pessoa de Meia-Idade , Idoso , Compostos Radiofarmacêuticos/uso terapêuticoRESUMO
Our objective was to demonstrate primarily the safety and secondarily the efficacy of 90Y glass microspheres in selective internal radiation therapy (SIRT) for hepatocellular carcinoma (HCC) in a local Southeast Asian hospital. Methods: Eleven consecutive patients with small, unresectable, nonmetastatic HCC and referred for locoregional therapy with SIRT with a curative intention were followed up for 6 mo after the procedure by way of interviews, blood tests, and anatomic scans. Results: Although 5 patients had deranged liver function tests after the procedure, in only 1 patient did this constitute a grade 1 toxicity (in alkaline phosphatase) by the Common Terminology Criteria for Adverse Events. Half the patients showed a reduction in serum α-fetoprotein measurements, and 6 of 11 patients demonstrated an objective response (complete or partial) on imaging. Conclusion: SIRT with 90Y glass microspheres is a safe and efficacious locoregional therapy for unresectable HCC. There are similar articles published in the West; however, the patient population there comprises far fewer Asians and the underlying cause for HCC is different from that in the Asian population. Despite these differences, SIRT is an equally effective and safe option for such patients.
Assuntos
Carcinoma Hepatocelular , Vidro , Neoplasias Hepáticas , Microesferas , Radioisótopos de Ítrio , Humanos , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/radioterapia , Radioisótopos de Ítrio/uso terapêutico , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Resultado do Tratamento , Segurança , Sudeste Asiático , População do Sudeste AsiáticoRESUMO
OBJECTIVES: To compare the survival and objective response rate (ORR) of the patients receiving estimated tumour absorbed dose (ETAD) <140 Gy versus ETAD ≥140 Gy in patients with advanced chemorefractory colorectal carcinoma liver metastases (CRCLM) treated with yttrium-90 transarterial radioembolization (90Y TARE). METHODS: Between August 2016 and August 2023 adult patients with unresectable, chemorefractory CRCLM treated with 90Y TARE using glass particles, were retrospectively enrolled. Primary outcomes were overall survival (OS) and hepatic progression free survival (hPFS). Secondary outcome was ORR. RESULTS: A total of 40 patients with a mean age of 66.2 ± 7.8 years met the inclusion criteria. Mean ETAD for group 1 (ETAD <140 Gy) and group 2 (ETAD ≥140) were 131.2 ± 17.4 Gy versus 195 ± 45.6 Gy, respectively. The mean OS and hPFS for group 1 versus group 2 were 12 ± 10.3 months and 8.1 ± 9.3 months versus 9.3 ± 3 months and 7.1 ± 8.4 months, respectively and there were no significant differences (P = .181 and P = .366, respectively). ORR did not show significant difference between the groups (P = .432). CONCLUSION: In real-world practice, no significant difference was found in OS, hPFS, and ORR between patients who received ETAD <140 Gy versus ETAD ≥140 Gy in patients with CRCLM, in this series. ADVANCES IN KNOWLEDGE: This study demonstrated that increased tumour absorbed doses in radioembolization may not provide additional significant advantage for OS and hPFS for patients with CRCLM.