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1.
Eur Radiol ; 33(3): 1801-1811, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36329348

RESUMO

BACKGROUND: There is growing evidence that partial nephrectomy (PN) and percutaneous cryoablation (PCA) yield comparable outcomes for patients with cT1a renal cell carcinoma (RCC), although the cost-effectiveness of both treatments still needs to be assessed. PURPOSE: To perform a cost-effectiveness analysis of PN and PCA for patients with cT1a RCC. MATERIALS AND METHODS: A decision analysis was created over a 5-year span from a healthcare payer's perspective computing expected costs and outcomes of PN and PCA in terms of quality-adjusted life-years (QALYs) and incremental cost-effectiveness (ICER). After each treatment, the following states were modelled using data from the recent literature: procedural complications, no evidence of disease (NED), local recurrence, metastases, and death from RCC- or non-RCC-related causes. Probabilistic and deterministic sensitivity analyses were performed. RESULTS: PCA and PN yielded health benefits of 3.68 QALY and 3.67 QALY. Overall expected costs were $20,491 and $26,478 for PCA and PN. On probabilistic sensitivity analysis, PCA was more cost-effective than PN in 84.78% of Monte Carlo simulations. PCA was more cost-effective until its complication risk was at least 38% higher than PN. PCA was more cost-effective than PN when (i) PCAs annual local recurrence risk was < 3.5% higher than that of PN in absolute values; (ii) PCAs annual metastatic risk was < 1.0% higher than that of PN; or (iii) PCAs annual cancer-specific mortality risk < 0.65% higher than that of PN. PCA remained cost-effective until its procedural cost is above $13,875. CONCLUSION: PCA appears to be more cost-effective than PN for the treatment of cT1a RCC, although the currently available evidence is of limited quality. PCA may be the better treatment strategy in the majority of scenarios varying procedural complications, recurrence, metastatic risk, and RCC-mortality in clinically plausible ranges. KEY POINTS: • For patients with cT1a RCCs, PCA yields a comparable health benefit at lower costs compared to PN, making PCA the dominant and therefore more cost-effective treatment strategy over PN. • PCA was more cost-effective than PN when (i) PCAs annual local recurrence risk was < 3.5% higher than PN in absolute values; (ii) PCAs annual metastatic risk was < 1.0% higher than PN; or (iii) PCAs annual cancer-specific mortality risk < 0.65% higher than PN. • PCA is more cost-effective than PN for the treatment of cT1a RCC, and it remained so in the majority of scenarios varying procedural complications, recurrence, metastatic risk, and RCC mortality.


Assuntos
Carcinoma de Células Renais , Criocirurgia , Neoplasias Renais , Humanos , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/secundário , Neoplasias Renais/cirurgia , Neoplasias Renais/patologia , Análise Custo-Benefício , Criocirurgia/efeitos adversos , Nefrectomia , Resultado do Tratamento
2.
J Vasc Interv Radiol ; 33(8): 964-971.e2, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35490932

RESUMO

PURPOSE: To assess the cost effectiveness of microwave ablation (MWA) and stereotactic body radiotherapy (SBRT) for patients with inoperable stage I non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: A literature search was performed in MEDLINE with broad search clusters. A decision-analytic model was constructed over a 5-year period. The model incorporated treatment-related complications and long-term recurrence. All clinical parameters were derived from the literature with preference to long-term prospective trials. A healthcare payers' perspective was adopted. Outcomes were measured in quality-adjusted life years (QALYs) extracted from prior studies and U.S. dollars from Medicare reimbursements and prior studies. Base case calculations, probabilistic sensitivity analysis with 10,000 Monte Carlo simulations, and multiple 1- and 2-way sensitivity analyses were performed. RESULTS: MWA yielded a health benefit of 2.31 QALYs at a cost of $195,331, whereas SBRT yielded a health benefit of 2.33 QALYs at a cost of $225,271. The incremental cost-effectiveness ratio was $1,480,597/QALY, indicating that MWA is the more cost-effective strategy. The conclusion remains unchanged in probabilistic sensitivity analysis with MWA being the optimal cost strategy in 99.84% simulations. One-way sensitivity analyses revealed that MWA remains cost effective when its annual recurrence risk is <18.4% averaged over 5 years, when the SBRT annual recurrence risk is >1.44% averaged over 5 years, or when MWA is at least $7,500 cheaper than SBRT. CONCLUSIONS: MWA appears to be more cost effective than SBRT for patients with inoperable stage I NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Idoso , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Análise Custo-Benefício , Humanos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Cadeias de Markov , Medicare , Micro-Ondas/efeitos adversos , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , Radiocirurgia/efeitos adversos , Estados Unidos
3.
Future Oncol ; 18(14): 1691-1703, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35172633

RESUMO

Objective: To evaluate the utilization and outcomes of PD-1-directed immunotherapy (PD-1 IMT) for advanced hepatocellular carcinoma. Methods: Patients with advanced hepatocellular carcinoma receiving systemic therapy and PD-1 IMT (nivolumab/pembrolizumab) were included from the Flatiron database. Overall survival (OS) was evaluated using multivariable Cox models with the following subgroup analyses: patients with data on clinical performance and liver function and patients receiving tyrosine kinase inhibitors. Results: n = 1770 patients were included (PD-1 IMT 19.3%). Overall, PD-1 IMT was associated with longer OS (hazard ratio [HR]: 0.57). This effect was robust across both subgroup analyses with HR: 0.72 (subgroup 1) and HR: 0.57 (subgroup 2). Conclusions: PD-1 IMT is increasingly used in clinical practice and associated with an OS benefit.


PD-1-directed immunotherapy (PD-1 IMT) is increasingly used for the treatment of advanced hepatocellular carcinoma in the USA. Patients receiving PD-1 IMT demonstrate a favorable overall survival compared with those without PD-1 IMT treatment.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Receptor de Morte Celular Programada 1 , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/patologia , Humanos , Fatores Imunológicos/uso terapêutico , Imunoterapia/estatística & dados numéricos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/patologia , Terapia de Alvo Molecular , Nivolumabe/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/imunologia , Estados Unidos
4.
Radiology ; 301(3): 533-540, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34581627

RESUMO

There is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue.


Assuntos
Técnicas de Ablação/métodos , Neoplasias/cirurgia , Consenso , Humanos , Reprodutibilidade dos Testes , Sociedades Médicas
5.
J Natl Compr Canc Netw ; 19(3): 307-318, 2021 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33530058

RESUMO

BACKGROUND: This study sought to assess microsatellite and KRAS status, prevalence, and impact on outcome in stage IV colorectal cancer (CRC). MATERIALS AND METHODS: The 2010 to 2016 US National Cancer Database was queried for adult patients with stage IV CRC. Prevalence of microsatellite status (microsatellite instability-high [MSI-H] or microsatellite stable [MSS]) and KRAS status (KRAS mutation or wild-type) of the primary CRC was assessed. Overall survival (OS) was evaluated using multivariable Cox proportional hazards models in patients with complete data on both microsatellite and KRAS status and information on follow-up. RESULTS: Information on microsatellite and KRAS status was available for 10,844 and 25,712 patients, respectively, and OS data were available for 5,904 patients. The overall prevalence of MSI-H status and KRAS mutation was 3.1% and 42.4%, respectively. Prevalence of MSI-H ranged between 1.6% (rectosigmoid junction) and 5.2% (transverse colon), and between 34.7% (sigmoid colon) and 58.2% (cecum) for KRAS mutation. MSI-H rates were highest in East North Central US states (4.1%), and KRAS mutation rates were highest in West South Central US states (44.1%). Multivariable analyses revealed longer OS for patients with KRAS wild-type versus mutation status (hazard ratio [HR], 0.91; 95% CI, 0.85-0.97; P=.004), those with MSS versus MSI-H status (HR, 0.75; 95% CI, 0.62-0.9; P=.003), and those with left-sided versus right-sided CRC (multivariable HR, 0.65; 95% CI, 0.6-0.7; P<.001). The effect of KRAS mutation further varied with CRC site and microsatellite status (P=.002 for interaction). CONCLUSIONS: Depending on the primary site and US geography, stage IV CRC shows distinct mutational behavior. KRAS mutation, MSI-H, and primary CRC sidedness independently affect OS and interact with distinct prognostic profiles. Generically classifying adenocarcinomas at different sites as CRC might deprecate this diversity.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Proteínas Proto-Oncogênicas p21(ras) , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Humanos , Mutação , Estadiamento de Neoplasias , Prevalência , Prognóstico , Proteínas Proto-Oncogênicas p21(ras)/genética , Estados Unidos
6.
J Vasc Interv Radiol ; 32(7): 1022-1028.e4, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33811997

RESUMO

PURPOSE: To assess whether the effectiveness of thermal ablation (TA) and stereotactic body radiotherapy (SBRT) as initial treatments for stage I lung cancer varies depending on the histological subtype. MATERIALS AND METHODS: The 2004-2016 National Cancer Database was queried for patients with American Joint Committee on Cancer stage I lung cancer treated with TA or SBRT. Patients <18 years, those treated with surgery or chemotherapy, or those with unknown survival and follow-up were excluded. TA and SBRT patients were 1:5 propensity score matched separately for each histological subtype to adjust for confounders. Overall survival (OS) was assessed using Cox models. RESULTS: A total of 28,425 patients were included (SBRT, n = 27,478; TA, n = 947). TA was more likely to be used in Caucasian patients, those with more comorbidities and smaller neuroendocrine tumors (NETs) of the lower lobe, and those whose treatment had taken place in the northeastern United States. After propensity score matching, a cohort with 4,085 SBRT and 817 TA patients with balanced confounders was obtained. In this cohort, OS for TA and SBRT was comparable (hazard ratio = 1.07; 95% confidence interval,0.98-1.18; P = .13), although it varied by histological subtypes: higher OS for TA was observed in patients with non-small cell NETs (vs SBRT hazard ratio = 0.48; 95% confidence interval, 0.24-0.95; P = .04). No significant OS differences between TA and SBRT were noted for adenocarcinomas, squamous cell carcinomas, small cell carcinomas, and non-neuroendocrine large cell carcinomas (each, P > .1). CONCLUSIONS: OS following TA and SBRT for stage I lung cancer is comparable for most histological subtypes, except that OS is longer after TA in non-small cell NETs.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/cirurgia , Estadiamento de Neoplasias , Resultado do Tratamento
7.
J Vasc Interv Radiol ; 31(4): 564-571, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32127324

RESUMO

PURPOSE: To assess use of stereotactic body radiotherapy (SBRT) for stage I renal cell carcinoma (RCC) and compare outcomes with thermal ablation and partial nephrectomy (PN). MATERIALS AND METHODS: The 2004-2015 National Cancer Database was investigated for histopathologically proven stage I RCC treated with PN, cryoablation, radiofrequency (RF) or microwave (MW) ablation, or SBRT. Patients were propensity score-matched to account for potential confounders, including patient age, sex, race, comorbidities, tumor size, histology, grade, tumor sequence, administration of systemic therapy, treatment in academic vs nonacademic centers, treatment location, and year of diagnosis. Overall survival (OS) was evaluated with Kaplan-Meier plots, log-rank tests, and Cox proportional hazards models. RESULTS: A total of 91,965 patients were identified (SBRT, n = 174; PN, n = 82,913; cryoablation, n = 5,446; RF/MW ablation, n = 3,432). Stage I patients who received SBRT tended to be older women with few comorbidities treated at nonacademic centers in New England states. After propensity score matching, a cohort of 636 patients was obtained with well-balanced confounders between treatment groups. In the matched cohort, OS after SBRT was inferior to OS after PN and thermal ablation (PN vs SBRT, hazard ratio [HR] = 0.29, 95% confidence interval [CI] 0.19-0.46, P < .001; cryoablation vs SBRT, HR = 0.40, 95% CI 0.26-0.60, P < .001; RF/MW ablation vs SBRT, HR = 0.46, 95% CI 0.31-0.67, P < .001). Compared with PN, neither cryoablation nor RF/MW ablation showed significant difference in OS (cryoablation vs PN, HR = 1.35, 95% CI 0.80-2.28, P = .258; RF/MW ablation vs PN, HR = 0.64, 95% CI 0.95-2.55, P = .079). CONCLUSIONS: Current SBRT protocols show lower OS compared with thermal ablation and PN, whereas thermal ablation and PN demonstrate comparable outcomes.


Assuntos
Técnicas de Ablação/tendências , Carcinoma de Células Renais/radioterapia , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/radioterapia , Neoplasias Renais/cirurgia , Nefrectomia/tendências , Padrões de Prática Médica/tendências , Radiocirurgia/tendências , Técnicas de Ablação/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/epidemiologia , Carcinoma de Células Renais/patologia , Ablação por Cateter/tendências , Criocirurgia/tendências , Bases de Dados Factuais , Feminino , Humanos , Neoplasias Renais/epidemiologia , Neoplasias Renais/patologia , Masculino , Micro-Ondas/uso terapêutico , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Lesões por Radiação/epidemiologia , Radiocirurgia/efeitos adversos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
J Vasc Interv Radiol ; 31(6): 953-960, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32376182

RESUMO

PURPOSE: To investigate the impact of direct-acting antivirals (DAAs) and 12-week sustained virologic response (SVR12) in patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) treated by interventional oncology (IO) therapies. MATERIALS AND METHODS: Retrospective analysis of patients diagnosed from 2005 to 2016 with HCC and receiving IO therapies. A total of 478 patients met inclusion criteria. Patients were age 29-90 years (mean 63.6 ± 9.4 years) and 78.9% (n =3 77) male. Two hundred and eighty-five (57%) patients had chronic HCV, 93 (33%) received DAAs, and 63 (68%) achieved SVR12. Liver function, tumor characteristics, and IO therapy including ablation, image-guided transcatheter tumor therapies (ITTT) (eg, chemoembolization and radioembolization), and combination locoregional therapy were assessed in analysis. RESULTS: Median overall survival (OS) of the cohort was 26.7 months (95% confidence interval [CI] 21.9-29.9). OS for ablation, combination locoregional therapy and ITTT, was 37.3 (CI 30.7-49.9), 29.3 (CI 24.2-38.0), and 19.7 months (CI 16.5-22.8), respectively (P < .0001). OS in patients with HCV was 30.7 months (CI 24.2-35.2) versus 22.2 months in non-HCV patients (CI 17.8-27.8, P = .03). Patients with HCV who received DAA had higher survival, 49.2 months (CI 36.5-not reached) versus those not receiving DAA, 18.5 months (CI 14.1-25.3, P < .0001). OS was 71.8 months (CI 42.3-not reached) for patients who achieved SVR12 after DAA versus 26.7 months in the non-SVR12 group (CI 15.9-31.1, P < .0001). Multivariable analysis revealed independent factors for OS including IO treatment type, DAA use and achieving SVR12 (P < .05). CONCLUSIONS: DAA use and SVR12 is associated with higher OS in patients with HCV-related HCC treated by IO therapies.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/terapia , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Neoplasias Hepáticas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/efeitos adversos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus/patogenicidade , Hepatite C/diagnóstico , Hepatite C/mortalidade , Hepatite C/virologia , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resposta Viral Sustentada , Fatores de Tempo , Resultado do Tratamento
9.
Ann Surg Oncol ; 26(7): 1993-2000, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30693451

RESUMO

OBJECTIVE: The aim of this study was to evaluate socioeconomic discrepancies in current treatment approaches and survival trends among patients with intrahepatic cholangiocarcinoma (ICC). METHODS: The 2004-2015 National Cancer Database was retrospectively analyzed for histopathologically proven ICC. Treatment predictors were evaluated using multinomial logistic regression and overall survival via multivariable Cox models. RESULTS: Overall, 12,837 ICC patients were included. Multiple factors influenced treatment allocation, including age, education, comorbidities, cancer stage, grade, treatment center, and US state region (multivariable p < 0.05). The highest surgery rates were observed in the Middle Atlantic (28.7%) and lowest rates were observed in the Mountain States (18.4%). Decreased ICC treatment likelihood was observed for male African Americans with Medicaid insurance and those with low income (multivariable p < 0.05). Socioeconomic treatment discrepancies translated into decreased overall survival for patients of male sex (vs. female; hazard ratio [HR] 1.21, 95% confidence interval [CI] 1.16-1.26, p < 0.001), with low income (< $37,999 vs. ≥ $63,000 annually; HR 1.07, 95% CI 1.01-1.14, p = 0.032), and with Medicaid insurance (vs. private insurance; HR 1.13, 95% CI 1.04-1.23, p = 0.006). Both surgical and non-surgical ICC management showed increased survival compared with no treatment, with the longest survival for surgery (5-year overall survival for surgery, 33.5%; interventional oncology, 11.8%; radiation oncology/chemotherapy, 4.4%; no treatment, 3.3%). Among non-surgically treated patients, interventional oncology yielded the longest survival versus radiation oncology/chemotherapy (HR 0.73, 95% CI 0.65-0.82, p < 0.001). CONCLUSIONS: ICC treatment allocation and outcome demonstrated a marked variation depending on socioeconomic status, demography, cancer factors, and US geography. Healthcare providers should address these discrepancies by providing surgery and interventional oncology as first-line treatment to all eligible patients, with special attention to the vulnerable populations identified in this study.


Assuntos
Neoplasias dos Ductos Biliares/economia , Neoplasias dos Ductos Biliares/mortalidade , Colangiocarcinoma/economia , Colangiocarcinoma/mortalidade , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/estatística & dados numéricos , Classe Social , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/terapia , Terapia Combinada , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos
10.
Eur Radiol ; 29(5): 2679-2689, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30560364

RESUMO

PURPOSE: To compare utilization and effectiveness of radiofrequency ablation (RFA) and surgical resection for hepatocellular carcinoma (HCC). METHODS: The 2004-2015 United States National Cancer Database was queried for HCC patients treated by RFA and surgical resection. Patients were 1:1 propensity score matched. Duration of hospital stay, unplanned readmission rates, and overall survival (OS) were compared in the matched cohort via multivariable regression models. RESULTS: Eighteen thousand two hundred ninety-six patients were included (RFA, n = 8211; surgical resection, n = 10,085). RFA was more likely in young male whites with high degree of hepatic fibrosis, high bilirubin levels, high INR, and multifocal HCC; resection was more likely in those with private insurance, high income, high cancer grade and stage, and larger HCC. RFA rates varied between 32.3% (East South Central) and 58.5% (New England). Post-treatment outcomes were superior for RFA versus resection regarding duration of hospital stay (median 1 vs. 5d, p < 0.001), 30-day unplanned hospital readmission rates (3.1% vs. 4.5%, p < 0.001), and 30-/90-day mortality (0% vs. 4.6%/8%, p < 0.001). Overall survival was comparable for RFA and resection for severe hepatic fibrosis/cirrhosis (5-year OS 37.3% vs. 39.4%, p = 0.07), for patients > 65 years old (5-year OS 21.9% vs. 26.5%, p = 0.47), and for HCC < 15 mm (5-year OS 49.7% vs. 52.3%, p = 0.78). OS in the full cohort was superior for surgical resection (5-year OS 29.9% vs. 45.7%, p < 0.01). CONCLUSION: RFA for HCC shows substantial variation by geography, socioeconomic factors, liver function, and tumor extent. RFA offers superior post-treatment outcomes versus surgical resection and may be an alternative for older patients with cirrhosis and/or small HCC. KEY POINTS: • Duration of hospital stay, unplanned readmissions, and 30-/90-day mortality are lower for RFA versus surgical resection. • RFA and surgical resection show similar survival in severe hepatic fibrosis. • In HCC < 15 mm, RFA and surgical resection yield similar survival.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter/métodos , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Pontuação de Propensão , Sistema de Registros , Adulto , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiologia , Feminino , Humanos , Incidência , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Estados Unidos/epidemiologia
11.
Eur Radiol ; 29(3): 1293-1307, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30255245

RESUMO

PURPOSE: To compare partial nephrectomy (PN), radiofrequency ablation (RFA), cryoablation (CRA) and microwave ablation (MWA) regarding oncologic, perioperative and functional outcomes. MATERIAL AND METHODS: The MEDLINE, EMBASE and COCHRANE libraries were searched for studies comparing PN, RFA, CRA or MWA and reporting on any-cause or cancer-specific mortality, local recurrence, complications or renal function. Network meta-analyses were performed. RESULTS: Forty-seven studies with 24,077 patients were included. Patients receiving RFA, CRA or MWA were older and had more comorbidities compared with PN. All-cause mortality was higher for CRA and RFA compared with PN (incidence rate ratio IRR = 2.58, IRR = 2.58, p < 0.001, respectively). No significant differences in cancer-specific mortality were evident. Local recurrence was higher for CRA, RFA and MWA compared with PN (IRR = 4.13, IRR = 1.79, IRR = 2.52, p < 0.05 respectively). A decline in renal function was less pronounced after RFA versus PN, CRA and MWA (mean difference in GFR MD = 6.49; MD = 5.82; MD = 10.89, p < 0.05 respectively). CONCLUSION: Higher overall survival and local control of PN compared with ablative therapies did not translate into significantly better cancer-specific mortality. Most studies carried a high risk of bias by selecting younger and healthier patients for PN, which may drive superior survival and local control. Physicians should be aware of the lack of high-quality evidence and the potential benefits of ablative techniques for certain patients, including a superior complication profile and renal function preservation. KEY POINTS: • Patients selected for ablation of small renal masses are older and have more comorbidities compared with those undergoing partial nephrectomy. • Partial nephrectomy yields lower all-cause mortality, which is probably biased by patient selection and does not translate into prolonged cancer-free survival. • The decline of renal function is smallest after radiofrequency ablation for small renal masses.


Assuntos
Técnicas de Ablação/métodos , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Humanos , Metanálise em Rede , Seleção de Pacientes , Resultado do Tratamento
12.
J Vasc Interv Radiol ; 30(3): 293-297, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30819468

RESUMO

PURPOSE: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. MATERIALS AND METHODS: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. RESULTS: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). CONCLUSIONS: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival.


Assuntos
Neoplasias dos Ductos Biliares/economia , Neoplasias dos Ductos Biliares/radioterapia , Quimiorradioterapia/economia , Colangiocarcinoma/economia , Colangiocarcinoma/radioterapia , Embolização Terapêutica/economia , Custos de Cuidados de Saúde , Medicare/economia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/economia , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/economia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/economia , Neoplasias dos Ductos Biliares/patologia , Quimiorradioterapia/efeitos adversos , Colangiocarcinoma/patologia , Análise Custo-Benefício , Bases de Dados Factuais , Custos de Medicamentos , Embolização Terapêutica/efeitos adversos , Feminino , Humanos , Masculino , Compostos Radiofarmacêuticos/efeitos adversos , Estudos Retrospectivos , Programa de SEER , Fatores de Tempo , Resultado do Tratamento , Estados Unidos , Radioisótopos de Ítrio/efeitos adversos
13.
Cancer ; 124(9): 1992-2000, 2018 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-29451701

RESUMO

BACKGROUND: Neuroendocrine tumors (NETs) metastasize to the liver. Everolimus and selective internal radioembolization (SIRT) are approved treatments. Pasireotide is a somatostatin analogue with an affinity for somatostatin receptors 1, 2, 3, and 5. Everolimus and pasireotide may potentiate SIRT radiosensitization and inhibit rebound angiogenesis. This study evaluated the safety of pasireotide, everolimus, and SIRT. METHODS: This 3 + 3 phase 1 trial evaluated 3 dose levels of everolimus (2.5, 5, and 10 mg/day), pasireotide (600 µg twice daily), and SIRT (SIR-Spheres dose on days 9 and 37). Eligibility criteria included well or moderately differentiated NETs, bilobar liver metastases, and progression on long-acting octreotide. Toxicities and responses were evaluated with the Common Terminology Criteria for Adverse Events and the Response Evaluation Criteria in Solid Tumors (version 1.1). Dose-limiting toxicities (DLTs) were defined in the first 28 days. Correlative markers-angiopoietin 1, angiopoietin 2, basic fibroblast growth factor, collagen V, insulin-like growth factor binding protein 1, insulin-like growth factor binding protein 1, interleukin 8, M30, M65, placenta growth factor, and vascular endothelial growth factor receptor 2-were assessed. The Norfolk Quality of Life-Neuroendocrine Tumor Questionnaire was used to assess the quality of life (QOL). RESULTS: Thirteen patients were enrolled; 1 was not evaluable for the primary endpoint. Eleven patients had well-differentiated tumors. The primary sites included small bowel (4), pancreas (3), lung (2), colon (1), gastric (1), and unknown primary (2) were unknown. Four had liver-only disease; 12 completed the planned treatment. No DLTs were observed. There was no treatment-related mortality. The most common toxicity was hyperglycemia. Clinically significant liver toxicity was not observed. One patient had liver progression. QOL improved on treatment. The median progression-free survival and overall survival were 18.6 and 46.3 months, respectively. CONCLUSIONS: The recommended phase 2 dose of everolimus is 10 mg daily in combination with pasireotide and SIRT. The regimen is well tolerated. Preliminary activity appears promising. Cancer 2018;124:1992-2000. © 2018 American Cancer Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Braquiterapia/métodos , Everolimo/administração & dosagem , Neoplasias Hepáticas/terapia , Tumores Neuroendócrinos/terapia , Somatostatina/análogos & derivados , Idoso , Braquiterapia/efeitos adversos , Quimiorradioterapia/métodos , Relação Dose-Resposta a Droga , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Feminino , Humanos , Estimativa de Kaplan-Meier , Fígado/irrigação sanguínea , Fígado/efeitos dos fármacos , Fígado/efeitos da radiação , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/etiologia , Tumores Neuroendócrinos/mortalidade , Tumores Neuroendócrinos/patologia , Intervalo Livre de Progressão , Qualidade de Vida , Critérios de Avaliação de Resposta em Tumores Sólidos , Somatostatina/administração & dosagem
14.
Radiology ; 288(3): 889-897, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29969077

RESUMO

Purpose To compare patients in a national U.S. database who underwent thermal ablation or nephrectomy for renal cell carcinoma (RCC) in terms of demographic differences, perioperative outcomes, and survival. Materials and Methods This National Cancer Database study included patients who underwent thermal ablation or nephrectomy for biopsy-proven T1aN0M0 RCC between 2004 and 2013. Demographic factors were analyzed as treatment predictors. Unplanned hospital readmission, mean hospital stay, 30- and 90-day postoperative mortality, and survival were analyzed in a propensity score-matched cohort by using χ2 tests, Cox proportional hazards models, and Renyi family tests. Results Included were 4817 of 56 065 patients (8.6%) who underwent thermal ablation and 51 248 of 56 065 patients (91.4%) who underwent nephrectomy. Patients who underwent thermal ablation skewed older (mean, 52 years vs 44 years, respectively) with more comorbidities (9% vs 7.6% Charlson Comorbidity Index score of ≥2, respectively). Male sex, white race, nonprivate insurance, therapy at academic centers, and south Atlantic state urban residence with lower income and education were associated with higher thermal ablation treatment likelihood (P < .001). After matching, perioperative outcomes were superior for thermal ablation: unplanned hospital readmission, mean hospital stay, and 30- and 90-day postoperative mortality were lower for thermal ablation (2% vs 3.3%, 1.3 days vs 4.3 days, 0% vs 0.9%, and 0% vs 1.4%, respectively; each P < .001). Survival was comparable for thermal ablation and nephrectomy in patients older than 65 years, and during the 1st postoperative year for all patients. Conclusion Thermal ablation for RCC varied by national region and with multiple clinical and nonclinical demographic factors. Thermal ablation demonstrates superior perioperative outcomes with short mean hospital stay, low unplanned hospital readmission, and 30- and 90-day mortality. In selected patients, thermal ablation survival may be comparable to nephrectomy.


Assuntos
Carcinoma de Células Renais/cirurgia , Ablação por Cateter/métodos , Neoplasias Renais/cirurgia , Tempo de Internação/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/epidemiologia , Estudos de Coortes , Feminino , Humanos , Rim/cirurgia , Neoplasias Renais/epidemiologia , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia , Adulto Jovem
15.
Radiology ; 288(1): 81-90, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29737950

RESUMO

Purpose To compare adverse events and survival outcomes, including cancer-specific survival and overall survival (OS), in patients with T1aN0M0 renal cell carcinoma (RCC) who are undergoing partial nephrectomy (PN), radical nephrectomy (RN), thermal ablation (TA), or active surveillance (AS). Materials and Methods Through use of the Surveillance, Epidemiology, and End Results-Medicare-linked database from 2002 to 2011 with at least 1 year of consecutive follow-up, a HIPAA-compliant retrospective propensity score-matched study of patients with T1aN0M0 RCC who underwent PN, RN, TA, or AS was performed. Medicare beneficiaries (n = 10 218) with T1aN0M0 RCC as first primary cancer diagnosis were included. Survival and adverse health outcomes were compared across treatment groups. Results Overall, cancer-specific survival significantly differed in the PN versus RN (P < .001), AS versus TA (P = .03), and AS versus PN (P = .002) groups. There were no significant differences when TA was compared with PN or RN, with 9-year cancer-specific survival rates of 96.4% versus 96.3% (PN vs TA, P = .07) and 96.1% versus 96.0% (RN vs TA, P = .14), respectively. With the exception of cancer-specific survival in AS versus RN groups (P = .29), cancer-specific survival and OS for all AS comparisons were significantly lower. In addition, compared with the patients undergoing TA, those in the PN and RN groups had increased rates of renal, cardiovascular, and thromboembolic adverse events up to 1 year after the procedure (P < .05 for all comparisons). Conclusion For T1aN0M0 RCC, TA confers cancer-specific survival and OS similar to those seen with surgical management, with significantly fewer adverse outcomes at 1 year after the procedure and similar rates of secondary cancer events compared with surgery.


Assuntos
Técnicas de Ablação/métodos , Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Medicare , Programa de SEER , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Rim/cirurgia , Masculino , Nefrectomia , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
16.
Radiology ; 289(3): 862-870, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30226453

RESUMO

Purpose To compare survival rates of thermal ablation and stereotactic radiation therapy (SRT) for stage 1 non-small cell lung cancer (NSCLC). Materials and Methods In this retrospective study, patients with stage 1 NSCLC treated by thermal ablation (TA) or SRT were identified in the 2004-2013 National Cancer Database. Patients who underwent TA and SRT were one-to-one propensity matched to undergo thermal ablation. Outcomes were overall survival and unplanned hospital readmission within 30 days after treatment. Results This study included 28 834 patients (TA, 1102 patients; SRT, 27 732 patients). Patients treated with TA had more comorbidities (Charlson comorbidity index of 1 vs ≥2, 32.8% [362 of 1102] vs 19.7% [217 of 1102], respectively) compared with SRT (Charlson comorbidity index of 1 vs ≥2, 26.9% [7448 of 27 732] vs 15.3% [4251 of 27 732], respectively; P , .001) and smaller tumor size (mean tumor size, TA vs SRT: 19 mm vs 22 mm, respectively; P , .001). In the propensity score-matched cohort with balanced distribution of potential confounders, there was no significant difference in overall survival between TA and SRT at a mean follow-up of 52.4 months (survival difference, P = .69). Overall survival rates were comparable between TA and SRT (1 year, 85.4% vs 86.3%, respectively, P = .76; 2 years, 65.2% vs 64.5%, respectively, P = .43; 3 years, 47.8% vs 45.9%, respectively, P = .32; 5 years, 24.6% vs 26.1%, respectively, P = .81). Unplanned hospital readmission rates were higher for patients who underwent TA versus those who underwent SRT (3.7% [40 of 1070] vs 0.2% [two of 1070], respectively; P , .001). Conclusion Regarding overall survival, thermal ablation was noninferior to stereotactic radiation therapy for primary treatment of stage 1 non-small cell lung cancer. © RSNA, 2018 Online supplemental material is available for this article. See also the editorial by Shyn in this issue.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Ablação por Cateter/métodos , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Radiocirurgia/métodos , Idoso , Estudos de Coortes , Bases de Dados Factuais , Feminino , Humanos , Pulmão/efeitos da radiação , Pulmão/cirurgia , Masculino , Pessoa de Meia-Idade , Readmissão do Paciente/estatística & dados numéricos , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Estados Unidos
17.
BMC Cancer ; 18(1): 75, 2018 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-29329568

RESUMO

BACKGROUND: To determine the effect of Yttrium-90 (Y90) radioembolization on health-related quality of life (HRQOL) and its effect on overall survival advanced, unresectable infiltrative hepatocellular carcinoma (HCC) patients with concurrent portal vein thrombosis (PVT). METHODS: Consecutive patients with unresectable infiltrative HCC and PVT were recruited. The Short-Form 36 (SF-36) questionnaire was used to assess HRQOL for consecutive patients treated with glass-based Y90 based on a prospective phase II trial. MR imaging was used to determine tumor progression every 3 months post-treatment. Overall survival (OS) from treatment and time to progression (TTP) was analyzed using Kaplan-Meier estimation and log-rank test. RESULTS: Thirty patients were treated and followed for 17.4 months; physical and mental component summary scores (PCS & MCS) remained unchanged at one, three, and six months. While no difference was observed in baseline SF-36 scores for patients with prolonged TTP (≥4 months) and OS (≥ 6 months), corresponding 1-month PCS were significantly higher than those with TTP < 4 months and OS < 6 months. At 1 month, patients with normalized Physical Function (PF), Role Physical (RP) and PCS within 2 standard deviations (SD) of US normalized baseline scores had a significantly prolonged median OS (15.7 vs. 3.7 months; p < 0.001) and TTP (12.4 vs. 1.8 mo; p < 0.001) compared those with physical component scores greater than 2SD below normalized US population values. CONCLUSION: Y90 radioembolization for HCC demonstrated long-term preservation of HRQOL. Lower baseline HRQOL scores were predictive of poorer OS. Early (1 month post-treatment) significant decreases in PCS were independent predictors of poorer OS and TTP. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01556282 , registered March 16, 2012.


Assuntos
Carcinoma Hepatocelular/radioterapia , Embolização Terapêutica , Neoplasias Hepáticas/radioterapia , Trombose Venosa/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/métodos , Carcinoma Hepatocelular/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Veia Porta/efeitos da radiação , Qualidade de Vida , Resultado do Tratamento , Trombose Venosa/patologia , Radioisótopos de Ítrio/administração & dosagem , Radioisótopos de Ítrio/efeitos adversos
18.
J Clin Gastroenterol ; 52(3): 262-267, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-28617762

RESUMO

BACKGROUND: Primary liver cancer, including Hepatoblastoma (HB) and hepatocellular carcinoma (HCC), in pediatric populations is often fatal. The outcomes are poor despite universal health care access in pediatric patients. AIM: We investigated the sociodemographic factors affecting outcomes in pediatric patients with primary liver cancer. MATERIALS AND METHODS: This is a large population database study of Surveillance, Epidemiology, and End Results cancer registry data from 1973 to 2011. HB and HCC were analyzed regarding age, sex, race, geographic area, and treatment-related information including survival. RESULTS: In total, 998 patients, the median age at time of diagnosis was 1 year for HB [0-19; 95% confidence interval (CI), 1.5-1.9] and 14 years for HCC (0-19; 95% CI, 12.1-13.3) (P<0.001). Overall Survival (OS) in HB was 374 months (25% failures 19) versus HCC 21 months (25% failures 5; P<0.0001). In HCC, the fibrolamellar subgroup OS was 41 months (32-.) versus 16 months (11-21) in all others [hazard ratio (HR) 2.0; P=0.005]. Diagnosis between 2000 and 2011 (HB: 25% failures not reached; HCC: 38) versus diagnosis 1973 to 1999 (HB: 374; HCC: 12) had different survival (P=0.01; HR 1.9). For HB, OS in patients with age of diagnosis under 2, 25% failures was not reached versus 374 months over the age of 2 (HR 1.7; P<0.0007). African American children with HB had OS of 67 (17-.) versus all others (25% failures 21) and 48% of African American children were diagnosed after the age of 2 versus 34% of whites (HR 1.9; P=0.01). CONCLUSIONS: Later diagnosis and decreased survival in African American children with HB warrants further research.


Assuntos
Carcinoma Hepatocelular/epidemiologia , Hepatoblastoma/epidemiologia , Neoplasias Hepáticas/epidemiologia , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Fatores Etários , Carcinoma Hepatocelular/etnologia , Carcinoma Hepatocelular/patologia , Criança , Pré-Escolar , Feminino , Acessibilidade aos Serviços de Saúde , Disparidades nos Níveis de Saúde , Hepatoblastoma/etnologia , Hepatoblastoma/patologia , Humanos , Incidência , Lactente , Recém-Nascido , Neoplasias Hepáticas/etnologia , Neoplasias Hepáticas/patologia , Masculino , Modelos de Riscos Proporcionais , Grupos Raciais/estatística & dados numéricos , Programa de SEER , Taxa de Sobrevida , Fatores de Tempo , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos , Adulto Jovem
19.
Radiology ; 282(3): 869-879, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-27673508

RESUMO

Purpose To evaluate the influence of bridging local-regional therapy (LRT) on hepatocellular carcinoma (HCC) recurrence and overall survival after orthotopic liver transplantation and to identify factors that predict HCC recurrence after orthotopic liver transplantation. Materials and Methods The United Network for Organ Sharing database was used to identify patients with HCC who underwent liver transplantation between 2002 and 2013. Patients with complete explant data within the Milan criteria for whom a Model for End-Stage Liver Disease exception was approved were retrospectively analyzed. Kaplan-Meier estimation was used for survival analysis with log-rank test and Cox proportional hazard models to assess independent prognostic factors for overall survival. Propensity-matched analysis for treatment groups was performed to minimize selection bias. Results The rate of tumor recurrence after liver transplantation was 11.5% (321 of 2794), which significantly decreased overall survival (P < .001). The bridging LRT group exhibited lower recurrence (59 of 686 [8.6%]; P = .02) and longer median overall survival (75.9 months; P < .001). Recurrence was higher in patients older than 60 years, serum α1-fetoprotein greater than 400 mg/L, bilobar distribution, multiple lesions, absent necrosis, microvascular invasion, and tumors beyond the Milan criteria (P < .05). Age, LRT status, serum α1-fetoprotein, and microvascular invasion were independent risk factors (P < .05). In the matched cohort, similar factors that predicted recurrence were observed (P < .05), whereas bridging LRT (P = .03) and serum α1-fetoprotein (P = .02) were independent risk factors for recurrence. Conclusion LRT significantly decreased tumor recurrence and lengthened overall survival. © RSNA, 2016.


Assuntos
Carcinoma Hepatocelular/terapia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Recidiva Local de Neoplasia/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Adulto , Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/cirurgia , Masculino , Estudos Retrospectivos , Fatores de Risco
20.
Mol Pharm ; 14(8): 2824-2830, 2017 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-28700244

RESUMO

The purpose of this article is to evaluate feasibility and safety of the cancer targeting (radio)-chemoembolization drug-eluting bead (TRCE-DEB) concept drug SW43-DOX-L-NETA(89Y) DEB for the intra-arterial treatment of VX2 rabbit liver tumors. The treatment compound comprises of the sigma-2 receptor ligand SW43 for cancer targeting, doxorubicin (DOX), and 89yttrium (89Y) as nonradioactive surrogate for therapeutic (yttrium-90, lutetium-177) and imaging (yttrium-86) radioisotopes via the chelator L-NETA. Ten New Zealand white rabbits with VX2 tumor allografts were used. SW43-DOX-89Y was synthesized, loaded onto DEB (100 µL; 100-300 µm), and administered intra-arterially in six rabbits at increasing doses (0.2-1.0 mg/kg). As controls, two rabbits each received either doxorubicin IV (0.3 mg/kg) or no treatment. Consecutive serum analysis for safety and histopathological evaluation after sacrifice were performed. One-Way ANOVA incl. Bonferroni Post-Hoc test was performed to compare groups. Targeted compound synthesis, loading onto DEB, and intra-arterial administration were feasible and successful in all cases. Serum liver enzyme levels increased in a dose dependent manner within 24 h and normalized within 3 days for 0.2/0.6 mg/kg SW43-DOX-89Y loaded onto DEB. The two rabbits treated with 1 mg/kg SW43-DOX-89Y had to be euthanized after 3/24 h due to worsening general condition. Histopathological necrosis increased over time in a dose depended manner with 95-100% tumor necrosis 3-7 days post treatment (0.6 mg/kg). SW43-DOX-89Y loaded onto DEB can be formulated and safely administered at a concentration of 0.6 mg/kg. Loading with radioactive isotopes (e.g., 86yttrium/90yttrium/177lutetium) to synthesize the targeted radio-chemoembolization drug-eluting bead (TRCE-DEB) concept drug is feasible.


Assuntos
Doxorrubicina/química , Doxorrubicina/uso terapêutico , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Ítrio/química , Ítrio/uso terapêutico , Análise de Variância , Animais , Modelos Animais de Doenças , Doxorrubicina/efeitos adversos , Sistemas de Liberação de Medicamentos/métodos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas Experimentais/sangue , Coelhos , Receptores sigma/metabolismo , Resultado do Tratamento , Ítrio/efeitos adversos
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