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1.
Thorac Cancer ; 14(26): 2696-2706, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37553772

RESUMEN

BACKGROUND: This study aimed to utilize an innovative method of integrating the 20 subvolume dose of left ventricle and the Tl-201 single photon emission computed tomography (SPECT) with myocardial perfusion imaging (MPI) parameters in patients with left- and right-sided breast cancer after radiation therapy. METHODS: Female patients with breast cancer underwent SPECT MPI before commencing radiotherapy and 12 months later were enrolled from January 2014 to December 2018. The images of CT simulation and SPECT MPI were integrated into the treatment planning system. The differences of doses and parameters of MPI in all cardiac subvolumes between left- and right-sided breast cancer patients were analyzed. RESULTS: Patients with left-sided breast cancer (n = 61) received a higher radiation dose to the heart, left ventricular, and its territories and subvolumes, compared to patients with right-sided breast cancer (n = 19). The 20-segment analysis also showed statistically significant disparities in the average radiation doses received by the two groups. In different coronary artery territories, the end-diastolic perfusion and end-systolic perfusion showed a decrease in both sides, with no significant differences. However, the wall motion and wall thickening showed a significant decline in subregions within the left- and right-sided coronary artery territories. CONCLUSION: This study demonstrates an innovative integrated method combining the left ventricular 20 regional doses with SPECT MPI which shows that left-sided breast cancer patients receive a higher subvolume dose than right-sided breast cancer patients. Further research is needed to confirm the potential impact on heart function after radiotherapy on both sides.


Asunto(s)
Neoplasias de la Mama , Imagen de Perfusión Miocárdica , Neoplasias de Mama Unilaterales , Humanos , Femenino , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Radioisótopos de Talio , Imagen de Perfusión Miocárdica/métodos
2.
Sci Rep ; 13(1): 10578, 2023 06 29.
Artículo en Inglés | MEDLINE | ID: mdl-37386034

RESUMEN

Adjuvant breast radiotherapy could reduce the risk of local recurrence. However, the radiation dose received by the heart also increases the risk of cardiotoxicity and causes consequential heart diseases. This prospective study aimed to evaluate more precisely cardiac subvolume doses and corresponding myocardial perfusion defects according to the American Heart Association (AHA)'s 20-segment model for single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) interpretation for breast cancer after radiotherapy. The 61 female patients who underwent adjuvant radiotherapy following breast cancer surgery for left breast cancer were enrolled. SPECT MPI were performed before radiotherapy for baseline study, and 12 months after for follow-up. Enrolled patients were divided into two groups, new perfusion defect (NPD) and non new perfusion defect found (non-NPD) according to myocardial perfusion scale score. CT simulation data, radiation treatment planning, and SPECT MPI images were fused and registered. The left ventricle was divided into four rings, three territories, and 20 segments according to the AHA's 20-segment model of the LV. The doses between NPD and non-NPD groups were compared by the Mann-Whitney test. The patients were divided into two groups: NPD group (n = 28) and non-NPD group (n = 33). The mean heart dose was 3.14 Gy in the NPD group and 3.08 Gy in the non-NPD group. Mean LV doses were 4.84 Gy and 4.71 Gy, respectively. The radiation dose of the NPD group was higher than the non-NPD group in the 20 segments of LV. There was significant difference in segment 3 (p = 0.03). The study indicated that the radiation doses to 20 segments of LV in NPD were higher than those in non-NPD significantly at segment 3, and higher in other segments in general. In the bull's eye plot combining radiation dose and NPD area, we found that the new cardiac perfusion decline may exist even in the low radiation dose region.Trial registration: FEMH-IRB-101085-F. Registered 01/01/2013, https://clinicaltrials.gov/ct2/show/NCT01758419?cond=NCT01758419&draw=2&rank=1 .


Asunto(s)
Neoplasias de la Mama , Femenino , Humanos , Mama , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/radioterapia , Neoplasias de la Mama/cirugía , Corazón/diagnóstico por imagen , Perfusión , Estudios Prospectivos
3.
Br J Haematol ; 201(1): 75-85, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36480431

RESUMEN

The increased expression of programmed death-ligands 1 and 2 (PD-L1 and PD-L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD-L1 (sPD-L1) and soluble PD-L2 (sPD-L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD-L1 and sPD-L2 in 46 patients with PCNSL using enzyme-linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD-L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD-L1 also exhibited superior overall discrimination performance compared to CSF sPD-L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD-L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep-brain involvement. Furthermore, CSF sPD-L1 could predict poor survival in PCNSL but CSF sPD-L2 could not. Intriguingly, CSF sPD-L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD-L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD-L1 blockade in PCNSL.


Asunto(s)
Antígeno B7-H1 , Linfoma , Humanos , Antígeno B7-H1/metabolismo , Pronóstico , Sistema Nervioso Central , Linfoma/diagnóstico
4.
Clin Cancer Res ; 28(23): 5058-5065, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36129471

RESUMEN

PURPOSE: Satisfactory treatment options for advanced leiomyosarcoma and liposarcoma are limited. The LEADER study (NCT03526679) investigated the safety and efficacy of lenvatinib plus eribulin. METHODS: LEADER is a multicenter phase Ib/II study for advanced leiomyosarcoma or liposarcoma. The phase Ib part enrolled 6 patients to determine the dose-limiting toxicity (DLT) and recommended phase II dose (RP2D) with the starting dose of lenvatinib 18 mg/day and eribulin 1.1 mg/m2 D1, D8 every 21 days. The primary endpoint of the phase II part was objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors 1.1, with phase Ib patients preplanned to be included in the efficacy analysis. Translational analyses were based on the transcriptomic data obtained from the NanoString nCounter platform. RESULTS: Thirty patients were enrolled (leiomyosarcoma 21, liposarcoma 9); the median age was 59. One patient had to temporarily stop lenvatinib due to grade 2 arthritis in the first cycle, meeting DLT criteria. Four of 6 patients had to decrease the dose of lenvatinib to 14 mg between cycles two and three. RP2D was determined at lenvatinib 14 mg/day and eribulin 1.1 mg/m2. The confirmed ORR was 20%, and the ORR was not significantly different between phase Ib/II cohorts (P = 0.23). The median progression-free survival was 8.56 months (95% confidence interval, 4.40-not reached). Translational studies suggested increased dendritic cells in the tumor microenvironment (TME) after treatment. CONCLUSIONS: Lenvatinib plus eribulin has a manageable safety profile and exhibits promising efficacy for treating advanced leiomyosarcoma and liposarcoma.


Asunto(s)
Leiomiosarcoma , Liposarcoma , Humanos , Persona de Mediana Edad , Cetonas/efectos adversos , Leiomiosarcoma/tratamiento farmacológico , Leiomiosarcoma/genética , Liposarcoma/tratamiento farmacológico , Liposarcoma/genética , Microambiente Tumoral
5.
Eur J Radiol ; 120: 108671, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31629121

RESUMEN

PURPOSE: To correlate the clinical stage and prognosis of oesophageal squamous cell carcinoma (SCC) using the imaging biomarkers from integrated positron emission tomography (PET)/magnetic resonance imaging (MRI). METHODS: In total, 54 consecutive patients with oesophageal SCC who receive PET/MRI scan were recruited before treatment. The imaging biomarkers used were the mean and minimal apparent diffusion coefficients (ADCmean and ADCmin), standardized uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of tumours. The correlation between each imaging biomarker and survival was investigated using the Cox proportional hazards model. RESULTS: ADCmean was negatively correlated with SUVmax (r = -0.414, P =  0.025). ADCmin was negatively correlated with SUVmax (r = -0.423, P =  0.001) and SUVpeak (r = -0.402, P =  0.003), and was significantly lower in M1 than in M0 tumours (829.6 vs. 1069.8, P = 0.005). MTV was significantly higher in T3 + (P <  0.001), N1 + (P = 0.014) and TNM stage III + (P <  0.001) tumours. TLG was significantly higher in T3 + (P <  0.001), N1 + (P <  0.001), M1 (P =  0.045) and TNM stage III + (P <  0.001) tumours. The MTV/ADCmin ratio exhibited the highest area under the receiver operating characteristic curve (AUROC) for predicting M1 and advanced TNM stage tumours. Multivariate analysis for progression-free survival (PFS) and overall survival (OS) showed that a larger MTV/ADCmin was associated with a shorter PFS and OS (P = 0.024 and 0.046, respectively). CONCLUSION: The imaging biomarkers in integrated PET/MRI may predict clinical stage and survival in patients with oesophageal SCC.


Asunto(s)
Neoplasias Esofágicas/diagnóstico , Carcinoma de Células Escamosas de Esófago/patología , Fluorodesoxiglucosa F18 , Radiofármacos , Adulto , Anciano , Anciano de 80 o más Años , Imagen de Difusión por Resonancia Magnética/métodos , Femenino , Glucólisis/fisiología , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Estadificación de Neoplasias , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Curva ROC , Estudios Retrospectivos , Carga Tumoral
6.
Eur Radiol ; 28(11): 4860-4870, 2018 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-29770848

RESUMEN

OBJECTIVES: The aim of this study is to investigate the correlation of survival outcomes with imaging biomarkers from multiparametric magnetic resonance imaging (MRI) in patients with brain metastases from breast cancer (BMBC). METHODS: This study was approved by the institutional review board. Twenty-two patients with BMBC who underwent treatment involving bevacizumab on day 1, etoposide on days 2-4, and cisplatin on day 2 in 21-day cycles were prospectively enrolled for a phase II study. Three brain MRIs were performed: before the treatment, on day 1, and on day 21. Eight imaging biomarkers were derived from dynamic contrast-enhanced MRI (Peak, IAUC60, Ktrans, kep, ve), diffusion-weighted imaging [apparent diffusion coefficient (ADC)], and MR spectroscopy (choline/N-acetylaspartate and choline/creatine ratios). The relative changes (Δ) in these biomarkers were correlated with the central nervous system (CNS)-specific progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier and Cox proportional hazard models. RESULTS: There were no significant differences in the survival outcomes as per the changes in the biomarkers on day 1. On day 21, those with a low ΔKtrans (p = 0.024) or ΔADC (p = 0.053) reduction had shorter CNS-specific PFS; further, those with a low ΔPeak (p = 0.012) or ΔIAUC60 (p = 0.04) reduction had shorter OS compared with those with high reductions. In multivariate analyses, ΔKtrans and ΔPeak were independent prognostic factors for CNS-specific PFS and OS, respectively, after controlling for age, size, hormone receptors, and performance status. CONCLUSIONS: Multiparametric MRI may help predict the survival outcomes in patients with BMBC. KEY POINTS: • Decreased angiogenesis after chemotherapy on day 21 indicated good survival outcome. • ΔK trans was an independent prognostic factors for CNS-specific PFS. • ΔPeak was an independent prognostic factors for OS. • Multiparametric MRI helps clinicians to assess patients with BMBC. • High-risk patients may benefit from more intensive follow-up or treatment strategies.


Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Antineoplásicos/uso terapéutico , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análisis , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/mortalidad , Colina/análisis , Creatinina/análisis , Femenino , Humanos , Estimación de Kaplan-Meier , Espectroscopía de Resonancia Magnética , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos
8.
Eur Radiol ; 27(7): 3069-3079, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-27957638

RESUMEN

OBJECTIVES: To correlate early changes in the parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) within 1 week of systemic therapy with overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Eighty-nine patients with advanced HCC underwent DCE-MRI before and within 1 week following systemic therapy. The relative changes of six DCE-MRI parameters (Peak, Slope, AUC, Ktrans, Kep and Ve) of the tumours were correlated with OS using the Kaplan-Meier model and the double-sided log-rank test. RESULTS: All patients died and the median survival was 174 days. Among the six DCE-MRI parameters, reductions in Peak, AUC, and Ktrans, were significantly correlated with one another. In addition, patients with a high Peak reduction following treatment had longer OS (P = 0.023) compared with those with a low Peak reduction. In multivariate analysis, a high Peak reduction was an independent favourable prognostic factor in all patients [hazard ratio (HR), 0.622; P = 0.038] after controlling for age, sex, treatment methods, tumour size and stage, and Eastern Cooperative Oncology Group performance status. CONCLUSIONS: Early perfusion changes within 1 week following systemic therapy measured by DCE-MRI may aid in the prediction of the clinical outcome in patients with advanced HCC. KEY POINTS: • DCE-MRI is helpful to evaluate perfusion changes of HCC after systemic treatment. • Early perfusion changes within 1 week after treatment may predict overall survival. • High Peak reduction was an independent favourable prognostic factor after systemic treatment.


Asunto(s)
Carcinoma Hepatocelular/irrigación sanguínea , Medios de Contraste/farmacología , Circulación Hepática/fisiología , Neoplasias Hepáticas/irrigación sanguínea , Angiografía por Resonancia Magnética/métodos , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Terapia Combinada , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Tasa de Supervivencia/tendencias , Taiwán/epidemiología , Factores de Tiempo , Adulto Joven
10.
BMC Cancer ; 16: 466, 2016 07 13.
Artículo en Inglés | MEDLINE | ID: mdl-27412562

RESUMEN

BACKGROUND: To determine the appropriate time of concomitant chemotherapy administration after antiangiogenic treatment, we investigated the timing and effect of bevacizumab administration on vascular normalization of metastatic brain tumors in breast cancer patients. METHODS: Eight patients who participated in a phase II trial for breast cancer-induced refractory brain metastases were enrolled and subjected to 4 dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) examinations that evaluated Peak, Slope, iAUC 60 , and Ktrans before and after treatment. The treatment comprised bevacizumab on Day 1, etoposide on Days 2-4, and cisplatin on Day 2 in a 21-day cycle for a maximum of 6 cycles. DCE-MRI was performed before treatment and at 1 h, 24 h, and 21 days after bevacizumab administration. RESULTS: Values of the 4 DCE-MRI parameters reduced after bevacizumab administration. Compared with baseline values, the mean reductions at 1 and 24 h were -12.8 and -24.7 % for Peak, -46.6 and -65.8 % for Slope, -27.9 and -55.5 % for iAUC 60 , and -46.6 and -63.9 % for Ktrans, respectively (all P < .05). The differences in the 1 and 24 h mean reductions were significant (all P < .05) for all the parameters. The generalized estimating equation linear regression analyses of the 4 DCE-MRI parameters revealed that vascular normalization peaked 24 h after bevacizumab administration. CONCLUSION: Bevacizumab induced vascular normalization of brain metastases in humans at 1 and 24 h after administration, and the effect was significantly higher at 24 h than at 1 h. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01281696 , registered prospectively on December 24, 2010.


Asunto(s)
Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Inhibidores de la Angiogénesis/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Bevacizumab/administración & dosificación , Neoplasias Encefálicas/irrigación sanguínea , Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/tratamiento farmacológico , Cisplatino/administración & dosificación , Cisplatino/uso terapéutico , Medios de Contraste/administración & dosificación , Esquema de Medicación , Resistencia a Antineoplásicos , Etopósido/administración & dosificación , Etopósido/uso terapéutico , Femenino , Humanos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Proyectos Piloto , Estudios Prospectivos , Factores de Tiempo , Resultado del Tratamiento
11.
Radiology ; 281(2): 454-464, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27171020

RESUMEN

Purpose To retrospectively compare the perfusion parameters of advanced hepatocellular carcinoma (HCC) measured with dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with surrounding liver parenchyma to determine the relationship between these parameters and uncensored overall survival (OS). Materials and Methods This retrospective study had institutional review board approval, and informed consent was waived. DCE MR imaging was performed in 92 patients with advanced HCC before systemic treatment was administered (19 patients received a placebo). Three semiquantitative (peak, slope, and area under the gadolinium concentration-time curve [AUC]) and six quantitative (arterial fraction, arterial flow, portal flow, total blood flow, distribution volume, and mean transit time) parameters were calculated by placing regions of interest in the largest area of the tumor and background liver parenchyma. The DCE MR imaging parameters between the tumor and normal liver were compared with paired Wilcoxon test. By using the Cox proportional hazards model for univariate and multivariate analyses, the association of DCE MR imaging parameters and OS was investigated. Results HCC demonstrated significantly higher peak, slope, AUC, arterial fraction, and arterial flow but lower portal flow, distribution volume, and mean transit time than did the background liver (all P < .05). Patients with high peak in the tumor had longer OS (P = .005) than did those with low peak. Cox multivariate analysis identified peak as an independent predictor of OS (P = .032) after adjusting for age, sex, treatment, tumor size, and portal vein thrombosis. Conclusion DCE MR imaging parameters can be used to differentiate advanced HCC from the background liver, and peak, a semiquantitative parameter, is associated with outcome in patients with advanced HCC before systemic therapy. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on July 22, 2016.


Asunto(s)
Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Medios de Contraste , Gadolinio DTPA , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Persona de Mediana Edad , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del Tratamiento
12.
Invest Radiol ; 47(11): 649-55, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23011189

RESUMEN

PURPOSE: The aim of this study was to evaluate the serial signal changes in hepatobiliary enhancement on gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid or gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging and its correlation with clinical parameters. METHOD: Under institutional review board approval, Gd-EOB-DTPA-enhanced magnetic resonance imaging was performed in 77 subjects (21 healthy volunteers and 56 biopsy-proven chronic hepatitis patients), and the signal intensities of the liver and common hepatic ducts (CHD) were measured every 2 minutes up to 50 minutes postcontrast. The associations among hepatic and CHD signals, physiological and hematological variables, histological activity index, and Metavir scores were analyzed with Pearson correlation and multiple linear stepwise regressions. The predictive ability of contrast enhancement index (CEI) of the liver with histological activity index and fibrosis scores at different time points were studied using nonparametric receiver operating characteristic curves. RESULTS: Among the clinical parameters, body weight and body mass index had the highest negative correlation with hepatobiliary enhancement between 2 and 50 minutes postcontrast (P < 0.001). Multiple regressions showed that creatinine level, body weight, and body mass index were independent predictors for both mean hepatic and CHD signal intensity (P < 0.05). Patients with more severe fibrosis or moderate necrosis tended to have lower CEIs than other patients were. The predictive ability of CEI for the best differentiation between no fibrosis and any fibrosis (F ≥ 1) was at 10 minutes postcontrast (area under the receiver operating characteristic curve, 0.797). CONCLUSIONS: Delayed hepatobiliary enhancement with Gd-EOB-DTPA could be possibly used for staging liver fibrosis. Contrast enhancement index of the liver at 10 minutes is useful for differentiating between no fibrosis and any degree of fibrosis in chronic hepatitis patients.


Asunto(s)
Conducto Colédoco/patología , Medios de Contraste , Gadolinio DTPA , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/patología , Hígado/patología , Imagen por Resonancia Magnética/métodos , Adulto , Índice de Masa Corporal , Femenino , Humanos , Masculino , Valor Predictivo de las Pruebas , Estudios Prospectivos , Intensificación de Imagen Radiográfica/métodos , Estadística como Asunto , Factores de Tiempo
13.
J Hepatol ; 56(5): 1097-1103, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22245891

RESUMEN

BACKGROUND & AIMS: Inhibitors of vascular endothelial growth factor receptor (VEGFR) and epidermal growth factor receptor (EGFR) have shown anti-tumor activities in advanced hepatocellular carcinoma (HCC). The present study evaluated the efficacy and safety of vandetanib, an oral inhibitor of both VEGFR and EGFR, in patients with unresectable advanced HCC. METHODS: Eligible patients were randomized 1:1:1 to receive vandetanib 300mg/day, vandetanib 100mg/day, or placebo. Upon disease progression, all patients had the option to receive open-label vandetanib 300mg/day. The primary objective was to evaluate tumor stabilization rate (complete response+partial response+stable disease ⩾4months). Secondary assessments included progression-free survival (PFS), overall survival (OS) and safety. Biomarker studies included circulating pro-angiogenic factors and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). RESULTS: Sixty-seven patients were randomized to vandetanib 300mg (n=19), vandetanib 100mg (n=25) or placebo (n=23) groups. Twenty-nine patients entered open-label treatment. Vandetanib induced a significant increase in circulating VEGF and decrease in circulating VEGFR levels. In both vandetanib arms, tumor stabilization rate was not significantly different from placebo: 5.3% (vandetanib 300mg), 16.0% (vandetanib 100mg) and 8.7% (placebo). DCE-MRI did not detect significant vascular change after vandetanib treatment. Although trends of improved PFS and OS after vandetanib treatment were found, they were statistically insignificant. The most common adverse events were diarrhea and rash, whose incidence did not differ significantly between treatment groups. CONCLUSIONS: Vandetanib has limited clinical activity in HCC. The safety profile was consistent with previous studies.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Piperidinas/uso terapéutico , Quinazolinas/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Antineoplásicos/efectos adversos , Antineoplásicos/farmacología , Carcinoma Hepatocelular/mortalidad , Método Doble Ciego , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/efectos de los fármacos , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Masculino , Persona de Mediana Edad , Piperidinas/efectos adversos , Piperidinas/farmacología , Quinazolinas/efectos adversos , Quinazolinas/farmacología , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/efectos de los fármacos , Tasa de Supervivencia , Resultado del Tratamiento
14.
J Hepatol ; 55(4): 858-65, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21338641

RESUMEN

BACKGROUND & AIMS: Sorafenib plus metronomic tegafur/uracil therapy can induce tumor stabilization in advanced hepatocellular carcinoma (HCC) patients. This study evaluated the correlation of vascular response measured by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and the clinical outcome. METHODS: DCE-MRI was performed in advanced HCC patients treated with sorafenib (800 mg/d) plus tegafur/uracil (250 mg/m(2)/d based on tegafur) at baseline and after 14 days of treatment. An operator-defined region of interest was placed in the most strongly enhanced area of the tumor to measure the pharmacokinetic parameter K(trans). Changes in K(trans) after treatment were correlated with the best tumor response and survival. RESULTS: Thirty-one patients were evaluable. There were one partial response (PR), 18 stable disease (SD), and 12 progressive disease (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST). Baseline K(trans) was higher in patients with PR or SD (median 1215.2 × 10(-3)/min, range 582.5-4555.3 × 10(-3)/min) than patients with PD (median 702.0 × 10(-3)/min, range 375.2-1938.0 × 10(-3)/min, p = 0.008). After 14 days of study treatment, the median K(trans) change was -47.1% (range -87.0 to -18.0%) in patients with PR or SD, and 9.6% (range -44.8 to +81%) in those with PD (p<0.001). A vascular response, defined by a 40% or greater decrease in K(trans) after 14 days of study treatment, correlated with longer progression-free survival (median 29.1 vs. 8.7 weeks, p = 0.033) and overall survival (median 53.0 vs. 14.9 weeks, p = 0.016). Percentage of K(trans) change after treatment is an independent predictor of tumor response, progression-free survival, and overall survival. CONCLUSIONS: K(trans) measured by DCE-MRI correlated well with tumor response and survival in HCC patients who received sorafenib plus metronomic tegafur/uracil therapy.


Asunto(s)
Bencenosulfonatos/administración & dosificación , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Piridinas/administración & dosificación , Tegafur/administración & dosificación , Uracilo/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Antimetabolitos Antineoplásicos/administración & dosificación , Antineoplásicos/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Biomarcadores , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Medios de Contraste , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/mortalidad , Neovascularización Patológica/patología , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Valor Predictivo de las Pruebas , Sorafenib , Adulto Joven
15.
Radiology ; 258(3): 821-31, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21212370

RESUMEN

PURPOSE: To examine whether dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging measurement of bone marrow perfusion in acute myeloid leukemia (AML) patients in complete remission (CR) is associated with outcome and survival. MATERIALS AND METHODS: After institutional review board approval and informed consent were obtained, from September 2004 to October 2007, 51 patients (29 women, 22 men; mean age, 43.5 years; range, 17-66 years) agreed to undergo DCE MR imaging to assess bone marrow perfusion, among 96 patients with newly diagnosed de novo AML who had received induction chemotherapy and achieved CR. Two semiquantitative parameters (peak and slope) and another three quantitative parameters (amplitude, K(ep) [efflux rate constant], and K(el) [elimination rate constant]) were calculated. Overall survival (OS) and relapse-free survival (RFS) were assessed with the Kaplan-Meier model, while differences between patient groups with high and low DCE MR imaging parameter values were assessed by using the two-sided log-rank test. RESULTS: The median follow-up was 25.9 months. Univariate analysis results showed that high values of peak (≥0.42), slope (≥0.0235), amplitude (≥0.03), and K(ep) (≥0.0082) were associated with shorter OS (P = .004, 0.01, 0.034, and 0.026, respectively). Besides, a high value of K(ep) was also associated with shorter RFS (P = .008). When age, sex, and initial karyotype at diagnosis were included in multivariate Cox proportional hazards analysis, the results showed that only K(ep), but not other DCE MR imaging parameters, was an independent factor for OS (relative risk [RR], 30.305; P = .021) and RFS (RR, 6.477; P = .009). CONCLUSION: Bone marrow perfusion measured with DCE MR imaging in AML patients in CR can be an indicator of outcome and survival. K(ep) measured with kinetic modeling was useful and significantly associated with RFS, while heuristic parameters (peak and slope) were not.


Asunto(s)
Médula Ósea/patología , Leucemia Mieloide Aguda/patología , Imagen por Resonancia Magnética/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Distribución de Chi-Cuadrado , Medios de Contraste , Femenino , Gadolinio DTPA , Humanos , Leucemia Mieloide Aguda/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Inducción de Remisión , Tasa de Supervivencia , Resultado del Tratamiento
16.
Blood ; 113(14): 3161-7, 2009 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-18988863

RESUMEN

Emerging evidence suggests that progression of hematologic malignancies is associated with angiogenesis. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can provide global and functional imaging of tumor angiogenesis. In this study, we performed bone marrow DCE-MRI prospectively at diagnosis and after induction chemotherapy in 78 de novo acute myeloid leukemia (AML) patients and correlated it with treatment outcome. An algorithm to assess bone marrow angiogenesis by measuring the DCE-MRI time-intensity curve pixel by pixel was developed using 3 distinct parameters: peak enhancement ratio (Peak) to indicate tissue blood perfusion; amplitude (Amp) to reflect vascularity; and volume transfer constant (K trans) to indicate vascular permeability. The Peak and Amp decreased significantly at remission status after induction chemotherapy. Patients with higher Peak or Amp at diagnosis had shorter overall survival and disease-free survival than others. Cox multivariate analysis identified higher Peak value (hazard ratio, 9.181; 95% confidence interval, 1.740-48.437; P = .009) as an independent predictor for overall survival in addition to unfavorable karyotype and old age. Our findings provide evidence that increased bone marrow angiogenesis measured by DCE-MRI can predict adverse clinical outcome in AML patients. DCE-MRI may help to select high-risk phenotype AML patients for tailored antiangiogenic therapy and to monitor treatment response.


Asunto(s)
Médula Ósea/irrigación sanguínea , Leucemia Mieloide Aguda/diagnóstico por imagen , Leucemia Mieloide Aguda/mortalidad , Neovascularización Patológica/diagnóstico por imagen , Adolescente , Adulto , Anciano , Médula Ósea/diagnóstico por imagen , Femenino , Trasplante de Células Madre Hematopoyéticas , Humanos , Leucemia Mieloide Aguda/patología , Leucemia Mieloide Aguda/terapia , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Pronóstico , Radiografía , Análisis de Supervivencia , Regulación hacia Arriba/fisiología , Adulto Joven
18.
Magn Reson Imaging ; 22(9): 1233-41, 2004 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-15607094

RESUMEN

OBJECTIVE: To characterize the findings of magnetic resonance imaging (MRI) of bacterial pyomyositis (PM) and correlate these data with the clinical information. MATERIALS AND METHODS: Eighty-one patients were diagnosed with PM in our institute between 1997 and 2003. Of these, 40 patients (21 male, 19 female; mean age, 53 years) also underwent MRI examination. The clinical manifestation underlying medical problems and the characteristics of MRI were analyzed. Thirty of the patients received surgical intervention or image-guided drainage/aspiration of the abscess along with administration of antibiotics, while the remaining 10 patients were promptly treated solely with antibiotics. RESULTS: Thirty-one of 40 patients had underlying medical problems. These involved diabetes mellitus (DM, n = 16), malignancies including cervical cancer, prostate cancer, non-Hodgkin's lymphoma and acute lymphocytic leukemia (n = 10, one case also had DM), autoimmune disease or asthma with long-term steroid usage (n = 4, one case also had DM), liver cirrhosis (n = 2) and chronic renal insufficiency (n = 1). Four patients had no abscess formation at presentation (invasive or early purulent stage), while the remaining 36 cases presented with at least one abscess (purulent stage). Patients older than 40 years or DM patients tended to have larger abscess(s) (P < .05). Gadolinium-enhanced images demonstrated either thick (n = 12) or thin rim enhancement (n = 24) of the abscess wall. For those 10 patients promptly treated solely with antibiotics, nine demonstrated thin rim enhancement of the abscess (P < .05). CONCLUSION: Magnetic resonance imaging plays an important role in the early recognition of bacterial PM. By precisely demarcating the extent of the disease, MRI can allow planning prompt antibiotic treatment combined with or without interventional procedures.


Asunto(s)
Infecciones Bacterianas/diagnóstico , Imagen por Resonancia Magnética/métodos , Músculo Esquelético/patología , Miositis/diagnóstico , Absceso/diagnóstico , Absceso/tratamiento farmacológico , Absceso/cirugía , Adulto , Anciano , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/cirugía , Distribución de Chi-Cuadrado , Niño , Preescolar , Medios de Contraste/administración & dosificación , Femenino , Gadolinio DTPA , Humanos , Aumento de la Imagen/métodos , Masculino , Persona de Mediana Edad , Músculo Esquelético/diagnóstico por imagen , Músculo Esquelético/cirugía , Miositis/tratamiento farmacológico , Miositis/cirugía , Variaciones Dependientes del Observador , Valor Predictivo de las Pruebas , Radiografía , Estudios Retrospectivos
19.
Pediatr Radiol ; 33(4): 266-8, 2003 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-12709759

RESUMEN

A cystic pancreatic tumour is rare in a child and a mature cystic teratoma of the pancreas is even rarer. This is the first demonstration of the CT appearance of such a tumour in a child. We present a 2-year-old boy who presented with a palpable abdominal mass. Abdominal CT revealed a huge cystic mass in the upper abdomen. Pathology disclosed a mature cystic teratoma originating from the pancreas.


Asunto(s)
Neoplasias Pancreáticas/diagnóstico por imagen , Teratoma/diagnóstico por imagen , Biopsia , Preescolar , Humanos , Masculino , Neoplasias Pancreáticas/patología , Teratoma/patología , Tomografía Computarizada por Rayos X
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