Monitoring early response to anti-angiogenic therapy: diffusion-weighted magnetic resonance imaging and volume measurements in colon carcinoma xenografts.
PLoS One
; 9(9): e106970, 2014.
Article
em En
| MEDLINE
| ID: mdl-25222284
ABSTRACT
OBJECTIVES:
To evaluate the use of diffusion-weighted MRI (DW-MRI) and volume measurements for early monitoring of antiangiogenic therapy in an experimental tumor model. MATERIALS ANDMETHODS:
23 athymic nude rats, bearing human colon carcinoma xenografts (HT-29) were examined before and after 6 days of treatment with regorafenib (nâ=â12) or placebo (nâ=â11) in a clinical 3-Tesla MRI. For DW-MRI, a single-shot EPI sequence with 9 b-values (10-800 s/mm2) was used. The apparent diffusion coefficient (ADC) was calculated voxelwise and its median value over a region of interest, covering the entire tumor, was defined as the tumor ADC. Tumor volume was determined using T2-weighted images. ADC and volume changes between first and second measurement were evaluated as classifiers by a receiver-operator-characteristic (ROC) analysis individually and combined using Fisher's linear discriminant analysis (FLDA).RESULTS:
All ADCs and volumes are stated as median±standard deviation. Tumor ADC increased significantly in the therapy group (0.76±0.09×10(-3) mm2/s to 0.90±0.12×10(-3) mm2/s; p<0.001), with significantly higher changes of tumor ADC than in the control group (0.10±0.11×10(-3) mm2/s vs. 0.03±0.09×10(-3) mm2/s; pâ=â0.027). Tumor volume increased significantly in both groups (therapy 347.8±449.1 to 405.3±823.6 mm3; pâ=â0.034; control 219.7±79.5 to 443.7±141.5 mm3; p<0.001), however, the therapy group showed significantly reduced tumor growth (33.30±47.30% vs. 96.43±31.66%; p<0.001). Area under the curve and accuracy of the ADC-based ROC analysis were 0.773 and 78.3%; and for the volume change 0.886 and 82.6%. The FLDA approach yielded an AUC of 0.985 and an accuracy of 95.7%.CONCLUSIONS:
Regorafenib therapy significantly increased tumor ADC after 6 days of treatment and also significantly reduced tumor growth. However, ROC analyses using each parameter individually revealed a lack of accuracy in discriminating between therapy and control group. The combination of both parameters using FLDA substantially improved diagnostic accuracy, thus highlighting the potential of multi-parameter MRI as an imaging biomarker for non-invasive early tumor therapy monitoring.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos de Fenilureia
/
Piridinas
/
Carcinoma
/
Neoplasias do Colo
/
Inibidores da Angiogênese
/
Imagem de Difusão por Ressonância Magnética
/
Xenoenxertos
Tipo de estudo:
Clinical_trials
/
Prognostic_studies
Limite:
Animals
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Female
/
Humans
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article