Assessment of changes in vascularity and blood volume in canine sarcomas and squamous cell carcinomas during fractionated radiation therapy using quantified contrast-enhanced power Doppler ultrasonography: a preliminary study.

Radiation therapy does not only target tumour cells but also affects tumour vascularity. In the present study, changes in tumour vascularity and blood volume were investigated in five grade 1 oral fibrosarcomas, eight other sarcomas (non-oral soft tissue and bone sarcomas) and 12 squamous cell carcinomas in dogs during fractionated radiation therapy (total dose, 45-56 Gy). Contrast-enhanced power Doppler ultrasound was performed before fraction 1, 3, 6, 8, 10, 12, 14 and 15 or 16 (sarcomas) or 17 (squamous cell carcinomas). Prior to treatment, median vascularity and blood volume were significantly higher in squamous cell carcinomas (P=0.0005 and 0.001), whereas measurements did not differ between oral fibrosarcomas and other sarcomas (P=0.88 and 0.999). During the course of radiation therapy, only small, non-significant changes in vascularity and blood volume were observed in all three tumour histology groups (P=0.08 and P=0.213), whereas median tumour volume significantly decreased until the end of treatment (P=0.04 for fibrosarcomas and other sarcomas, P=0.008 for squamous cell carcinomas). It appeared that there was a proportional decrease in tumour volume, vascularity and blood volume. Doppler measurements did not predict progression free interval or survival in any of the three tumour groups (P=0.06-0.86). However, the number of tumours investigated was small and therefore, the results can only be considered preliminary.

Correlation of quantified contrast-enhanced power Doppler ultrasonography with immunofluorescent analysis of microvessel density in spontaneous canine tumours.

Conventionally, tumour vascularity is assessed invasively by immunofluorescent analysis. Quantified contrast-enhanced power Doppler ultrasound has been used to measure tumour angiogenesis non-invasively in humans and experimental animals. The purpose of this study was to correlate quantified contrast-enhanced power Doppler ultrasound with immunofluorescent results in 45 spontaneous canine tumours. With power Doppler, mean vascularity was high in squamous cell carcinomas, moderate in malignant oral melanomas and low in sarcomas. There was high mean vascularity in squamous cell carcinomas and low mean vascularity in sarcomas and malignant oral melanomas. Although Doppler parameters correlated moderately with microvascular density for all tumours (P=0.004, r=0.4), they did not correlate within histology groups. These analyses show that vascularity differs among canine tumour histology groups. However, dependent on the method used, measurement of tumour vascularity can provide different biological information.

Correlation of pretreatment polarographically measured oxygen pressures with quantified contrast-enhanced power doppler ultrasonography in spontaneous canine tumors and their impact on outcome after radiation therapy.

PURPOSE: To evaluate the use of noninvasive quantified contrast-enhanced power Doppler ultrasonography as a surrogate in the estimation of tumor hypoxia measured by invasive pO(2) histography in canine tumors. MATERIAL AND METHODS: Data of pretreatment tumor oxygenation status, tumor vascularity and blood volume, and tumor response after radiation therapy was collected in 48 spontaneous malignant oral tumors (Table 1). Tumor oxygenation status was correlated to vascularity and blood volume, and influences on outcome after treatment were analyzed. RESULTS: Although vascularity and blood volume correlated moderately with median pO(2) (r = 0.51 and 0.61; p = 0.001 and < 0.0001) and percentage of pO(2) readings < or = 2.5, 5, and 10 mmHg (r = -0.37 to -0.42; p < 0.01-0.03) for all tumors, they did not correlate within the different histology groups (p = 0.06-0.9). For all tumors, pretreatment oxygenation status, vascularity and blood volume were not found to be of prognostic value (Tables 2 and 3). CONCLUSION: These analyses show that quantified contrast-enhanced power Doppler ultrasonography does not represent a noninvasive indirect method to assess tumor hypoxia measured by invasive pO(2) histography. Both technologies were nonprognostic indicators in spontaneous malignant canine oral tumors.

The influence of fractionated radiation therapy on plasma vascular endothelial growth factor (VEGF) concentration in dogs with spontaneous tumors and its impact on outcome.

BACKGROUND AND PURPOSE: Vascular endothelial growth factor (VEGF), a specific pro-angiogenic factor is proposed to be involved in cancer progression and resistance to radiation therapy by promoting angiogenesis and by protecting endothelial cells from radiation induced apoptosis. The aim of this study, was first to assess the influence of ionizing radiation on plasma VEGF concentration in spontaneous canine tumors during fractionated radiation therapy with curative or palliative intent and second to analyze plasma VEGF concentration as predictor for treatment outcome. PATIENTS AND METHODS: For plasma VEGF analysis a human VEGF enzyme linked immunosorbent assay was used. Sixty dogs with various tumor types were included in this study. Dogs were irradiated with either low dose per fx (3-3.5 Gy per fraction, total dose: 42-49 Gy, group A: curative intent) or high dose per fx (6-8 Gy per fraction, total dose: 24-30 Gy, group B: palliative intent). Blood samples were taken before and after dose application at certain time points during therapy. Follow-up evaluation was performed for analysis of time to treatment failure and survival. RESULTS: Repeated measures analysis showed no increase of plasma VEGF in dogs treated with fractionated radiation therapy (group A and B). Dichotomizing baseline plasma VEGF into two groups with high and low plasma VEGF, resulted in shorter time to treatment failure in dogs with high plasma VEGF levels (TTF, group A: P=0.038, group B: P=0.041). CONCLUSIONS: This study demonstrated that dogs with a plasma VEGF level higher than 5 pg/ml had a poorer outcome after radiation therapy. It is therefore, suggested, to use plasma VEGF as predictor for treatment outcome in radiation therapy.

Changes in vascularity and blood volume as a result of photodynamic therapy can be assessed with power Doppler ultrasonography.

BACKGROUND AND OBJECTIVES: One principal mechanism of photodynamic therapy (PDT) in tumors is destruction of tumor-associated vasculature. In the present study, the vascular effects of PDT in tumors were investigated with power Doppler ultrasonography. MATERIALS AND METHODS: Seven cutaneous squamous cell carcinomas in cats were treated. Tumors were examined via power Doppler ultrasonography before, 5 minutes, 1 hour, and 24 hours after PDT. Images were digitized for computer-aided assessment of vascularity and blood volume. RESULTS: Mean baseline tumor vascularity and blood volume were moderate. During PDT, a significant decrease in vascularity and blood volume was noted. Lowest values were found 24 hours after PDT. CONCLUSIONS: Power Doppler ultrasonography represents a non-invasive modality to successfully monitor the vascular effects and thus, treatment efficacy, of PDT.