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INTRODUCTION: Chordoma is a rare, aggressive tumor that is believed to originate from notochord remnants. It can occur anywhere from the clivus to the sacrum and often recurs even after resection and radiotherapy. We present a unique case that initially suggested a different pathology based on imaging and presentation but was found to be a chordoma on gross and pathological analysis. CASE PRESENTATION: An 11-year-old girl presented outpatient for scoliosis evaluation and was found to have what appeared to be a right L4 peripheral nerve sheath tumor on MRI, causing dextroconvex scoliosis. She underwent a gross total resection via a retroperitoneal approach and was found to have what appeared to be an extraosseous, extradural, extra-spinal canal lumbar chordoma. Immunohistochemical features on surgical pathology were consistent with chordoma. The patient was referred to radiation oncology for adjuvant radiotherapy and pediatric hematology/oncology for recurrence monitoring. DISCUSSION: Our case is the first to present in such a manner, was shown to be external to the spinal canal, encasing the nerve root, and was the first such case in a pediatric patient. We reviewed the growing body of literature on spinal extraosseous chordomas and their characteristics within the pediatric patient population. We also reviewed chordoma pathogenesis theories as well as current and future treatment options.
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Cordoma , Escoliose , Neoplasias da Coluna Vertebral , Feminino , Humanos , Criança , Cordoma/diagnóstico por imagem , Cordoma/cirurgia , Cordoma/patologia , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Neoplasias da Coluna Vertebral/cirurgia , Radioterapia Adjuvante , Imageamento por Ressonância MagnéticaRESUMO
PURPOSE: To analyze long-term outcomes in patients bridged/downstaged to orthotopic liver transplantation (OLT) by transarterial chemoembolization (TACE) or yttrium-90 radioembolization (Y90) for hepatocellular carcinoma (HCC). METHODS: 172 HCC patients who underwent OLT after being treated with transarterial liver-directed therapies (LDTs) (Y90: 93; TACE: 79) were identified. Pre-LDT and pre-OLT clinical/imaging/laboratory characteristics including United Network for Organ Sharing (UNOS) staging and alpha-fetoprotein values (AFP) were tabulated. Post-OLT HCC recurrence was assessed by imaging follow-up per standard of care. Recurrence-free (RFS) and overall survival (OS) were calculated. Uni/multivariate and sub-stratification analyses were performed. RESULTS: Time-to-OLT was longer in the Y90 group (Y90: 6.5 months; TACE: 4.8 months; p=0.02). With a median post-OLT follow-up of 26.1 months (IQR: 11.1-49.7), tumor recurrence was found in 6/79 (8%) TACE and 8/93 (9%) Y90 patients. Time-to-recurrence was 26.6 (CI: 7.0-49.5) and 15.9 months (CI: 7.8-46.8) for TACE and Y90, respectively (p=0.48). RFS (Y90: 79 months; TACE: 77 months; p=0.84) and OS (Y90: 57% alive at 100 months; TACE: 84.2 months; p=0.57) were similar. 54/155 patients (Y90: 29; TACE: 25) were downstaged to UNOS T2 or less. RFS hazard ratios for patients downstaged to ≤T2 versus those that were not were 0.6 (CI: 0.33-1.1) and 1.7 (CI: 0.9-3.1) respectively (p=0.13). 17/155 patients (Y90: 8; TACE: 9) that were >T2 were downstaged to UNOS T2 or less (within transplant criteria). Distribution (unilobar/bilobar), AFP, and pre-transplant UNOS stage affected RFS on univariate analyses. CONCLUSION: Despite longer time-to-OLT for Y90 patients, post-OLT outcomes were similar between patients bridged or downstaged by TACE or Y90. A trend towards improved RFS for downstaged patients was identified.
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Braquiterapia/métodos , Carcinoma Hepatocelular/patologia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/patologia , Transplante de Fígado/métodos , Recidiva Local de Neoplasia/patologia , Radioisótopos de Ítrio/química , alfa-Fetoproteínas/metabolismo , Humanos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , alfa-Fetoproteínas/químicaRESUMO
PURPOSE: The aim of this study was to analyze the safety, treatment characteristics and survival outcomes of Yttrium-90 (Y90) radioembolization for unresectable colorectal carcinoma (CRC) liver metastases refractory to standard of care therapy. METHODS: A total of 214 patients with CRC metastases were treated with Y90 radioembolization over 12 years. Toxicity was assessed using National Cancer Institute common terminology criteria. Overall survival was analyzed from date of diagnosis of primary cancer, hepatic metastases and from the first Y90. Uni/multivariate analyses were performed. Substratification by era of chemotherapeutics was performed. RESULTS: Most patients were male (60 %) and <65 years old (61 %). Of them, 98 % had been exposed to chemotherapy. Grade 3 lymphocyte, bilirubin, albumin, ALP and AST toxicities were observed in 39 %, 11 %, 10 %, 8 % and 4 % of patients, respectively. Grade 4 lymphocyte and ALP toxicities were observed in 5 % and 3 % of patients, respectively. Median overall survival was 43.0, 34.6, and 10.6 months from date of diagnosis of primary cancer, hepatic metastases and first Y90, respectively. Survival was significantly longer in patients: (1) who received ≤2 cytotoxic drugs (n = 104) than those who received 3 (n = 110) (15.2 vs. 7.5 months, p = 0.0001); and (2) who received no biologic agents (n = 52) compared with those that did (n = 162) (18.6 vs. 9.4 months, p = 0.0001). Multivariate analyses identified ≤2 cytotoxic agents, no exposure to biologics, ECOG 0, tumor burden <25 %, lack of extrahepatic disease and albumin >3 g/dL as independent predictors of survival. CONCLUSION: In this largest metastatic CRC series published to date, Y90 radioembolization was found to be safe; survival varied by prior therapy. Further studies are required to further refine the role of Y90 in metastatic CRC.
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Carcinoma/secundário , Quimiorradioterapia , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/terapia , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Idoso , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/efeitos adversos , Análise de Sobrevida , Radioisótopos de Ítrio/efeitos adversosRESUMO
PURPOSE: To investigate the predictive value of transcatheter intraarterial perfusion (TRIP) magnetic resonance (MR) imaging-measured tumor perfusion changes during transarterial chemoembolization on transplant-free survival (TFS) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This HIPAA-compliant prospective study was approved by the institutional review board. Written informed consent was obtained from all patients. Fifty-one consecutive adult patients with surgically unresectable single or multifocal measurable HCC and adequate laboratory parameters who underwent chemoembolization in a combined MR imaging-interventional radiology suite between February 2006 and June 2010 were studied. Tumor perfusion changes during chemoembolization were measured by using TRIP MR imaging with area under the time-signal intensity curve calculation. The end point of the study was TFS. The authors assessed the correlation between the percentage perfusion reduction in the tumor during chemoembolization and TFS by using univariate and multivariate analyses. RESULTS: Fifty patients (mean age, 61 years; 39 men aged 42-87 years [mean age, 61 years] and 11 women aged 49-83 years [mean age, 62 years]) were eligible for the analysis. Patients with 35%-85% intraprocedural tumor area under the time-signal intensity curve reduction (n = 32) showed significantly improved median TFS compared with patients with an area under the time-signal intensity curve reduction outside this range (n = 18) (16.6 months [95% confidence interval: 11.2, 22.0 months] vs 9.3 months [95% confidence interval: 6.6, 12.0 months], respectively; P = .046; hazard ratio: 0.46; 95% confidence interval: 0.21, 1.00). The cumulative TFS rates in the 35%-85% and less than 35% or more than 85% perfusion reduction groups at 1, 2, and 5 years after chemoembolization were 66.4%, 42.2%, and 28.2% versus 33.8%, 16.9%, and 0%, respectively. CONCLUSION: The study shows evidence of an association between intraprocedural tumor perfusion reduction during chemoembolization and TFS and suggests the utility of TRIP MR imaging- measured tumor perfusion reduction as an intraprocedural imaging biomarker during chemoembolization.
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Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica/métodos , Neoplasias Hepáticas/terapia , Angiografia por Ressonância Magnética/métodos , Imagem por Ressonância Magnética Intervencionista , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiografia Digital , Antineoplásicos/administração & dosagem , Biomarcadores , Biópsia , Meios de Contraste/administração & dosagem , Feminino , Gadolínio DTPA/administração & dosagem , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , Carga TumoralRESUMO
The aim of the study was to analyze the safety and efficacy of yttrium-90 ((90)Y) radioembolization in the treatment of unresectable hepatic melanoma metastases refractory to previous systemic/locoregional therapy. Between February 2004 and April 2010, 16 patients with hepatic melanoma metastases (ocular=7, skin=4, other sites=5) were treated with (90)Y radioembolization at a single center. Toxicity was assessed using the National Cancer Institute Common Terminology Criteria, version 3.0. Response to therapy was assessed by size and necrosis criteria. Progression-free survival (hepatic) and overall survival were calculated using the Kaplan-Meier method. The median dose to the treatment site was 108.57 Gy. Grade 1 and 2 clinical toxicities included fatigue (44%), nausea (19%), and vomiting (12%). Grade 3 absolute lymphocyte toxicity and aspartate aminotransferase toxicity were noted in 2 (12%) and 1 (7%) patients, respectively. Grade 4 bilirubin toxicity was observed in 1 (7%) patient. Overall, 13 (81%) patients showed disease control (response+stable disease) according to WHO, European Association for the Study of the Liver, and Response Evaluation Criteria for Solid Tumors. Progressive disease was observed in 3 (19%) patients according to WHO, European Association for the Study of the Liver, and Response Evaluation Criteria for Solid Tumors. The median overall and hepatic progression-free survival times were 7.63 and 4.23 months. Patients with disease control (responders+stable disease) survived longer than those with progressive disease (9.97 vs. 2.13 months, P<0.0001). Results from this small and single-center experience show that radioembolization is a safe therapy and its potential for being an efficacious therapy for hepatic melanoma metastases should be explored further. Radioembolization should be considered for liver-dominant disease refractory to other forms of systemic therapies.
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Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Melanoma/radioterapia , Melanoma/secundário , Compostos Radiofarmacêuticos/administração & dosagem , Neoplasias Cutâneas/patologia , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Chicago , Intervalo Livre de Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Masculino , Melanoma/mortalidade , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/efeitos adversos , Dosagem Radioterapêutica , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversosRESUMO
PURPOSE: To compare the utility of different staging systems and analyze independent predictors of survival in patients with hepatocellular carcinoma (HCC) treated with yttrium-90 ((90)Y) radioembolization. MATERIALS AND METHODS: During the period 2004-2011, 428 patients with HCC were treated with (90)Y radioembolization. All patients were staged prospectively by the following staging systems: Child-Turcotte-Pugh (CTP), United Network for Organ Sharing, Barcelona Clinic Liver Cancer (BCLC), Okuda classification, Cancer of the Liver Italian Program (CLIP), Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire, Chinese University Prognostic Index, and Japan Integrated Staging. The ability of the staging systems to predict survival was assessed. The staging systems were compared using Cox proportional hazards regression model, linear regression, Akaike information criterion (AIC), and concordance index (C-index). Univariate and multivariate analyses were employed to assess independent predictors of survival. RESULTS: When tested independently, all staging systems exhibited significant ability to discriminate early (long survival) from advanced (worse survival) disease. CLIP provided the most accurate information in predicting survival outcomes (AIC = 2,993, C-index = 0.8503); CTP was least informative (AIC = 3,074, C-index = 0.6445). Independent predictors of survival included Eastern Cooperative Oncology Group performance status grade 0 (hazard ration [HR], 0.56; confidence interval [CI], 0.34-0.93), noninfiltrative tumors (HR, 0.62; CI, 0.44-0.89), absence of portal venous thrombosis (HR, 0.60; CI, 0.40-0.89), absence of ascites (HR, 0.56; CI, 0.40-0.76), albumin ≥ 2.8 g/dL (HR, 0.72; CI, 0.55-0.94), alkaline phosphatase ≤ 200 U/L (HR, 0.68; CI, 0.50-0.92), and α-fetoprotein ≤ 200 ng/mL (HR, 0.67; CI, 0.51-0.86). CONCLUSIONS: CLIP was most accurate in predicting survival in patients with HCC. Given that not all patients receive the recommended BCLC treatment strategy, this information is relevant for clinical trial design and predicting long-term outcomes after (90)Y radioembolization.
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Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/radioterapia , Técnicas de Apoio para a Decisão , Embolização Terapêutica/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/radioterapia , Estadiamento de Neoplasias/métodos , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Idoso , Carcinoma Hepatocelular/mortalidade , Distribuição de Qui-Quadrado , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Lineares , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To validate our initial pilot study and confirm sustained safety and tumor response of extended-shelf-life (90)Y glass microspheres. We hypothesized that for the same planned tissue dose, the increase in number of glass microspheres (decayed to the second week of their allowable shelf-life) administered for the same absorbed dose would result in better tumor distribution of the microspheres without causing additional adverse events. METHODS: Between June 2007 and January 2010, 134 patients underwent radioembolization with extended-shelf-life (90)Y glass microspheres; data from 84 new patients were combined with data from our 50-patient pilot study cohort. Baseline and follow-up imaging and laboratory data were obtained 1 and 3 months after therapy and every 3 months thereafter. Clinical and biochemical toxicities were prospectively captured and categorized according to the Common Terminology Criteria. Response in the index lesion was assessed using WHO and EASL guidelines. RESULTS: The mean delivered radiation dose was 123 Gy to the target liver tissue. The mean increase in number of microspheres with this approach compared to standard (90)Y glass microsphere dosimetry was 103%, corresponding to an increase from 3.84 to 7.78 million microspheres. Clinical toxicities included fatigue (89 patients, 66%), abdominal pain (49 patients, 36.6%), and nausea/vomiting (25 patients, 18.7%). Grade 3/4 bilirubin toxicity was seen in three patients (2%). Two (1%) of the initial 50-patient cohort showed gastroduodenal ulcers; gastroduodenal ulcers were not seen in any of the subsequent 84 patients. According to WHO and EASL guidelines, response rates were 48% and 57%, respectively, and 21% demonstrated a complete EASL response. CONCLUSION: This study showed sustained safety and efficacy of extended-shelf-life (90)Y glass microspheres in a larger, 134-patient cohort. The increase in number of microspheres administered theoretically resulted in better tumor distribution of the microspheres without an increase in adverse events.
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Neoplasias dos Ductos Biliares/radioterapia , Carcinoma Hepatocelular/radioterapia , Colangiocarcinoma/radioterapia , Neoplasias Hepáticas/radioterapia , Microesferas , Compostos Radiofarmacêuticos/efeitos adversos , Radioisótopos de Ítrio/efeitos adversos , Idoso , Estabilidade de Medicamentos , Feminino , Seguimentos , Vidro , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêuticoAssuntos
Duodeno/irrigação sanguínea , Embolização Terapêutica/métodos , Vidro , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/radioterapia , Compostos Radiofarmacêuticos/administração & dosagem , Estômago/irrigação sanguínea , Radioisótopos de Ítrio/administração & dosagem , Artérias , Embolização Terapêutica/efeitos adversos , Humanos , Neoplasias Hepáticas/patologia , Microesferas , Compostos Radiofarmacêuticos/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversosRESUMO
BACKGROUND & AIMS: Portal vein embolization (PVE) is a standard technique for patients not amenable to liver resection due to small future liver remnant ratio (FLR). Radiation lobectomy (RL) with (90)Y-loaded microspheres (Y90) is hypothesized to induce comparable volumetric changes in liver lobes, while potentially controlling the liver tumor and limiting tumor progression in the untreated lobe. We aimed at testing this concept by performing a comprehensive time-dependent analysis of liver volumes following radioembolization. METHODS: 83 patients with right unilobar disease with hepatocellular carcinoma (HCC; N=67), cholangiocarcinoma (CC; N=8) or colorectal cancer (CRC; N=8) were treated by Y90 RL. The total liver volume, lobar (parenchymal) and tumor volumes, FLR and percentage of FLR hypertrophy from baseline (%FLR hypertrophy) were assessed on pre- and post-Y90 CT/MRI scans in a dynamic fashion. RESULTS: Right lobe atrophy (p=0.003), left lobe hypertrophy (p<0.001), and FLR hypertrophy (p<0.001) were observed 1 month after Y90 and this was consistent at all follow-up time points. Median %FLR hypertrophy reached 45% (5-186) after 9 months (p<0.001). The median maximal %FLR hypertrophy was 26% (-14 â 86). Portal vein thrombosis was correlated to %FLR hypertrophy (p=0.02). Median Child-Pugh score worsening (6 â 7) was seen at 1 to 3 months (p=0.03) and 3 to 6 months (p=0.05) after treatment. Five patients underwent successful right lobectomy (HCC N=3, CRC N=1, CC N=1) and 6 HCCs were transplanted. CONCLUSIONS: Radiation lobectomy by Y90 is a safe and effective technique to hypertrophy the FLR. Volumetric changes are comparable (albeit slightly slower) to PVE while the right lobe tumor is treated synchronously. This novel technique is of particular interest in the bridge-to-resection setting.
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Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Fígado/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Progressão da Doença , Feminino , Hepatectomia , Humanos , Fígado/efeitos da radiação , Fígado/cirurgia , Neoplasias Hepáticas/mortalidade , Imageamento por Ressonância Magnética , Masculino , Microesferas , Pessoa de Meia-Idade , Tamanho do Órgão , Taxa de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de ÍtrioRESUMO
A sophisticated understanding of the rapidly changing field of oncology, including a broad knowledge of oncologic disease and the therapies available to treat them, is fundamental to the interventional radiologist providing oncologic therapies, and is necessary to affirm interventional oncology as one of the four pillars of cancer care alongside medical, surgical, and radiation oncology. The first part of this review intends to provide a concise overview of the fundamentals of oncologic clinical trials, including trial design, methods to assess therapeutic response, common statistical analyses, and the levels of evidence provided by clinical trials.
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Ensaios Clínicos como Assunto/métodos , Oncologia/métodos , Neoplasias/terapia , Radiografia Intervencionista , Projetos de Pesquisa , Ensaios Clínicos como Assunto/estatística & dados numéricos , Intervalos de Confiança , Interpretação Estatística de Dados , Progressão da Doença , Intervalo Livre de Doença , Determinação de Ponto Final , Medicina Baseada em Evidências , Humanos , Estimativa de Kaplan-Meier , Oncologia/estatística & dados numéricos , Neoplasias/diagnóstico por imagem , Neoplasias/mortalidade , Neoplasias/patologia , Radiografia Intervencionista/estatística & dados numéricos , Projetos de Pesquisa/estatística & dados numéricos , Fatores de Tempo , Resultado do TratamentoRESUMO
This is the second of a two-part overview of the fundamentals of oncology for interventional radiologists. The first part focused on clinical trials, basic statistics, assessment of response, and overall concepts in oncology. This second part aims to review the methods of tumor characterization; principles of the oncology specialties, including medical, surgical, radiation, and interventional oncology; and current treatment paradigms for the most common cancers encountered in interventional oncology, along with the levels of evidence that guide these treatments.
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Oncologia/métodos , Neoplasias/terapia , Radiografia Intervencionista , Técnicas de Ablação , Cateterismo , Procedimentos Endovasculares , Medicina Baseada em Evidências , Humanos , Neoplasias/diagnóstico por imagem , Neoplasias/patologia , Guias de Prática Clínica como Assunto , Resultado do TratamentoRESUMO
PURPOSE: To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. METHODS: 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. RESULTS: Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. CONCLUSION: Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated.
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Embolização Terapêutica/métodos , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Compostos Radiofarmacêuticos/administração & dosagem , Radioisótopos de Ítrio/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/radioterapia , Masculino , Microesferas , Pessoa de Meia-Idade , Estudos Prospectivos , Compostos Radiofarmacêuticos/efeitos adversos , Análise de Sobrevida , Radioisótopos de Ítrio/efeitos adversosRESUMO
BACKGROUND & AIMS: Quality of life (QoL) is an important aspect of any palliative treatment. However, few data are available from studies comparing how embolotherapy affects QoL for patients with hepatocellular carcinoma (HCC). We performed a health-related QoL study in patients with HCC treated by transarterial chemoembolization (TACE) or (90)Y radioembolization. METHODS: We performed a prospective study of patients undergoing (90)Y radioembolization (n = 29) or TACE (n = 27) for HCC. We assessed patients before treatment and 2 and 4 weeks after treatment using the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) survey. We compared differences in health-related QoL between the treatment groups using linear regression repeated-measures analysis. RESULTS: At baseline, the groups had comparable baseline Child-Pugh class and performance statuses, although patients undergoing TACE had lower tumor burdens (P = .018) and less-advanced disease, based on United Network for Organ Sharing and Barcelona stage (P = .03 and P = .02, respectively), permitting injections at segmental arteries (P < .0001). There were no significant differences between groups in overall FACT-Hep health-related QoL scores (P = .055, effect size [ES], .54), owing to a limited sample size. Despite the more advanced disease of patients who received (90)Y radioembolization, they had a significantly better QoL, based on social well being (P = .019; ES, .65), functional well-being (P = .031; ES, .60), and embolotherapy-specific scores (P = .018; ES, .67). They also had a trend toward better overall QoL (P = .055; ES, .54) and higher Trial Outcome Index (P = .05; ES, .56) and FACT-Hep scores (P = .071; ES, .52). CONCLUSIONS: In a prospective study, although (90)Y radioembolization was used to treat patients with more advanced disease, those who received this treatment had significant increases in several features of QoL, whereas patients who received TACE had decreases in QoL scores. However, because of the limited sample size, there was no significant difference in overall FACT-Hep health-related QoL scores. The increase was greatest in the embolotherapy-specific score. ClinicalTrials.gov, number NCT00739167.
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Carcinoma Hepatocelular/psicologia , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/métodos , Qualidade de Vida/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
UNLABELLED: The aim of this study was to compare radiological and pathological changes and test the adjunct efficacy of Sorafenib to Y90 as a bridge to transplantation in hepatocellular carcinoma (HCC). 15 patients with 16 HCC lesions were randomized to Y90 without (Group A, n = 9) or with Sorafenib (Group B, n = 7). Size (WHO, RECIST), enhancement (EASL, mRECIST) and diffusion-weighted imaging criteria (apparent diffusion coefficient, ADC) measurements were obtained at baseline, then at 1 and every 3 months after treatment until transplantation. Percentage necrosis in explanted tumors was correlated with imaging findings. 100%, 50%-99% and <50% pathological necrosis was observed in 6 (67%), 1 (11%), and 2 (22%) tumors in Group A and 3 (42%), 2 (28%), and 2 (28%) in Group B, respectively (P = 0.81). While ADC (P = 0.46) did not change after treatment, WHO (P = 0.06) and RECIST (P = 0.08) response at 1 month failed to reach significance, but significant responses by EASL (P < 0.01/0.03) and mRECIST (P < 0.01/0.03) at 1 and 3 months were observed. Response was equivalent by EASL or mRECIST. No difference in response rates was observed between groups A and B at 1 and 3 months by WHO, RECIST, EASL, mRECIST or ADC measurements. Despite failing to reach significance, smaller baseline size was associated with complete pathological necrosis (CPN) (RECIST: P = 0.07; WHO: P = 0.05). However, a cut-off size of 35 mm was predictive of CPN (P = 0.005). CPN could not be predicted by WHO (P = 0.25 and 0.62), RECIST (P = 0.35 and 0.54), EASL (P = 0.49 and 0.46), mRECIST (P = 0.49 and 0.60) or ADC (P = 0.86 and 0.93). CONCLUSION: The adjunct of Sorafenib did not augment radiological or pathological response to Y90 therapy for HCC. Equivalent significant reduction in enhancement at 1 and 3 months by EASL/mRECIST was noted. Neither EASL nor mRECIST could reliably predict CPN.
Assuntos
Carcinoma Hepatocelular/terapia , Imagem de Difusão por Ressonância Magnética/métodos , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Idoso , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Microesferas , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Estudos Prospectivos , Sorafenibe , Agregado de Albumina Marcado com Tecnécio Tc 99m/administração & dosagem , Organização Mundial da SaúdeRESUMO
PURPOSE: To present data on safety, antitumoral response, and survival following yttrium-90 ((90)Y) radioembolization for patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: The present study expands on the cohort of 24 patients with ICC described in a pilot study, and includes 46 patients treated with (90)Y radioembolization at a single institution during an 8-year period. Via retrospective review of a prospectively collected database, patients were stratified by performance status, tumor distribution (solitary or multifocal), tumor morphology (infiltrative or peripheral), and presence/absence of portal vein thrombosis. Primary endpoints included biochemical and clinical toxicities, and secondary endpoints included imaging response (World Health Organization [WHO] and European Association for the Study of Liver Disease [EASL] criteria) and survival. Uni-/multivariate analyses were performed. RESULTS: Ninety-two treatments were performed, with a mean of two per patient. Fatigue and transient abdominal pain occurred in 25 patients (54%) and 13 patients (28%), respectively. Treatment-related gastroduodenal ulcer developed in one patient (2%). WHO imaging findings included partial response (n = 11; 25%), stable disease (n = 33; 73%), and progressive disease (n = 1; 2%). EASL imaging findings included partial/complete response (n = 33; 73%) and stable disease (n = 12; 27%). Survival varied based on presence of multifocal (5.7 mo vs 14.6 mo), infiltrative (6.1 mo vs 15.6 mo), and bilobar disease (10.9 mo vs 11.7 mo). Disease was converted to resectable status in five patients, who successfully underwent curative (ie, R0) resection. CONCLUSIONS: Radioembolization with (90)Y is safe and demonstrates antitumoral response and survival benefit in select patients with ICC. Results are most pronounced in patients with solitary tumors, for whom conversion to curative resection is possible.
Assuntos
Colangiocarcinoma/radioterapia , Embolização Terapêutica/métodos , Neoplasias Hepáticas/radioterapia , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Idoso , Neoplasias dos Ductos Biliares , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/mortalidade , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Progressão da Doença , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/mortalidade , Feminino , Hepatectomia , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/efeitos adversos , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversosRESUMO
PURPOSE: During the course of cancer treatment, patients whose disease progresses despite therapy are offered alternative options. Similarly, patients with hepatocellular carcinoma (HCC) whose disease progresses following arterial locoregional therapies (LRTs) cross over to undergo systemic therapies or participate in clinical trials. Per current guidelines, patients must meet inclusion criteria (most importantly Child-Pugh class A status) to qualify for systemic options. The present study analyzed the candidacy for systemic agents or clinical trials of patients whose disease progresses despite LRTs. MATERIALS AND METHODS: A total of 245 patients with HCC were treated with LRTs (chemoembolization, n = 123; yttrium-90 [(90)Y] radioembolization, n = 122) as part of a previously published comparative effectiveness study; 96 patients exhibiting disease progression were followed prospectively. Modes of progression (cancer stage, Child-Pugh class) were analyzed to determine candidacy for systemic therapy or clinical trials, as well as assess ultimate treatment(s) received. RESULTS: Among the 96 patients with disease progression, 52% and 48% had Child-Pugh class A and class B/C disease, respectively, thereby substantially limiting the latter group's eligibility for systemic therapy and/or clinical trials. Of those whose disease progressed who had advanced-stage HCC, 63% had Child-Pugh class B/C disease. By size and necrosis criteria, the local disease progression rate was higher with chemoembolization than with (90)Y radioembolization (P = .006 and P = .016, respectively). Of the 96 patients with disease progression, only 13 (13%) ultimately received systemic agents or entered clinical trials. CONCLUSIONS: Most patients with advanced HCC that progresses following LRTs were not candidates for clinical trials or systemic agents. There is a need for future research efforts directed at treatment options or novel trial designs that will permit inclusion of patients with progressive liver disease and suboptimal liver function.
Assuntos
Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Ensaios Clínicos como Assunto/métodos , Neoplasias Hepáticas/terapia , Seleção de Pacientes , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Distribuição de Qui-Quadrado , Progressão da Doença , Definição da Elegibilidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the toxicity and response to radioembolization with yttrium-90 ((90)Y) glass microspheres in patients with hepatocellular carcinoma (HCC) and existing transjugular intrahepatic portosystemic shunts (TIPS). MATERIALS AND METHODS: For treatment of unresectable HCC, 12 patients with a patent TIPS underwent a total of 21 infusions of (90)Y. Toxicity within 90 days of treatment was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v4.0). Imaging response within the index lesion was assessed using the World Health Organization (WHO) and European Association for the Study of the Liver (EASL) guidelines. Survival was calculated using the Kaplan-Meier method. RESULTS: All patients had a patent TIPS on imaging before treatment. Clinical toxicities included fatigue (83%), encephalopathy (33%), and abdominal pain (25%). Three patients (25%) experienced new grade 3 or 4 bilirubin toxicity. Imaging response was achieved in 50% and 67% of patients according to WHO and EASL criteria. Six patients (50%) went on to liver transplantation. Median survival censored for liver transplantation was 498 days (95% confidence interval [CI],100-800 d), and uncensored median survival was 827 days (95% CI, 250-2,400 d). CONCLUSIONS: (90)Y radioembolization may be a safe and effective treatment for patients with unresectable HCC and existing TIPS. This minimally embolic therapy may be particularly useful as a bridge to curative liver transplantation.
Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Radioisótopos de Ítrio/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Derivação Portossistêmica Transjugular Intra-Hepática , Compostos Radiofarmacêuticos/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND & AIMS: Yttrium-90 ((90)Y) radioembolization is a microembolic procedure. Hence, it is commonly used in hepatocellular carcinoma (HCC) patients with portal venous thrombosis (PVT). We analyzed liver function, imaging findings, and treatment options (local/systemic) at disease progression following (90)Y treatment in HCC patients with PVT. METHODS: We treated 291 HCC patients with (90)Y radioembolization. From this cohort, we included patients with liver-only disease, PVT and Child-Pugh (CP) score ≤ 7; this identified 63 patients with HCC and PVT (CP-A:35, CP-B7:27). Liver function, CP status, and imaging findings at progression were determined in order to assess potential candidacy for systemic treatment/clinical trials. Survival, time-to-progression (TTP), and time-to-hepatic decompensation analyses were performed using Kaplan-Meier methodology. RESULTS: Of 35 CP-A and 28 CP-B7 patients, 29 and 15 progressed, respectively. Median survival and TTP were 13.8 and 5.6 months in CP-A and 6.5 and 4.9 months in CP-B7 patients, respectively. Of the 29 CP-A patients who progressed, 45% maintained their CP status at progression (55% decompensated to CP-B). Of the 15 CP-B7 patients who progressed, 20% improved to CP-A, 20% maintained their CP score and 60% decompensated. CONCLUSIONS: Knowledge of liver function and CP score of HCC with PVT progressing after (90)Y is critically relevant information, as these patients may be considered for systemic therapy/clinical trials. If a strict CP-A status is mandated, our study demonstrated that 64% of cases exhibited inadequate liver function and were ineligible for systemic therapy/clinical trials. An adjuvant approach using local therapy and systemic agents prior to progression should be investigated.
Assuntos
Carcinoma Hepatocelular/radioterapia , Embolização Terapêutica/métodos , Cirrose Hepática/radioterapia , Neoplasias Hepáticas/radioterapia , Veia Porta , Trombose Venosa/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/mortalidade , Estudos de Coortes , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Cirrose Hepática/mortalidade , Testes de Função Hepática , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Trombose Venosa/mortalidade , Radioisótopos de Ítrio/uso terapêuticoRESUMO
Yttrium-90 microspheres are radioactive particles which are increasingly being employed for treating patients with unresectable hepatocellular carcinoma (HCC). The procedure is called radioembolization. It involves the injection of micron-sized embolic particles loaded with a radioisotope by use of transarterial techniques. Because of the sensitivity of liver parenchyma and relative insensitivity of tumor, external radiation has played a limited role in treating HCC. (90)Y administered via arterial route directs the highly concentrated radiation to the tumor while healthy liver parenchyma is relatively spared due to its preferential blood supply from portal venous blood. This technique has proven useful for the majority of patients with HCC as most of them present in advanced stage, beyond potentially curative options (resection/liver transplantation). (90)Y microspheres can be used in downstaging large tumors to bring within transplantable criteria, in patients with portal venous thrombosis due to tumor invasion and as palliative therapy. There are two available devices for (90)Y administration; TheraSphere® (glass based) and SIR-Spheres® (resin based). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, GI ulcers, and vascular injury; however, these can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article explores the technical and clinical aspects of (90)Y radioembolization with keeping emphasis on patient selection, uses, and complications.
Assuntos
Carcinoma Hepatocelular/radioterapia , Embolização Terapêutica , Neoplasias Hepáticas/radioterapia , Radioisótopos de Ítrio/uso terapêutico , Biomarcadores Tumorais , Carcinoma Hepatocelular/terapia , Embolização Terapêutica/efeitos adversos , Humanos , Infusões Intra-Arteriais/efeitos adversos , Fígado/irrigação sanguínea , Neoplasias Hepáticas/terapia , Microesferas , Seleção de Pacientes , Compostos Radiofarmacêuticos/uso terapêutico , Radioisótopos de Ítrio/efeitos adversosRESUMO
Hepatic metastatic disease includes tumors from colorectal, neuroendocrine, breast, melanocytes, kidney, and other primary sites. Tumor characteristic, liver function, and performance status are factors that need to be considered while deciding on treatment. Surgery offers the most optimal therapeutic option for such patients. However, due to the diffuse nature of disease and large tumor burden, a majority of the patients are not operable. Moreover, because the morbidity and mortality is associated with hepatic metastatic disease, it is intuitive to investigate and develop treatment options that target the tumor locally, thereby minimizing systemic toxicities. Transarterial locoregional therapies, such as chemoembolization and radioembolization, have been widely investigated during the past decade for the treatment of hepatic metastatic disease and have generated encouraging outcomes in term of survival, response, and quality of life. Moreover, these options are applicable in many clinical scenarios, because they are less limited by tumor characteristics. Currently, a large number of trials are investigating the combination of locoregional and systemic therapies, and the results are expected to benefit the treating physicians and patients alike.