Combining functional imaging and interstitial pressure measurements to evaluate two anti-angiogenic treatments.

BACKGROUND: Interstitial hypertension is responsible for poor capillary blood flow and hampered drug delivery. The efficacy of combined sorafenib/bevacizumab treatment given according to different administration schedules has been evaluated by measuring both interstitial pressure (IP) and quantitative dynamic contrast-enhanced ultrasonography (DCE-US) parameters in melanoma-bearing mice. MATERIAL AND METHODS: [corrected] Sixty mice were xenografted with B16F10 melanoma. Animals received a daily administration over 4 days (D0 to D3) of either sorafenib at 30 mg/kg, bevacizumab at 2.5 mg/kg alone, or different schedules of combined treatments. Perfusion parameters determined using an Aplio® sonograph (Toshiba) with SonoVue® contrast agent (Bracco) were compared to IP measurements using fiberoptic probes (Samba®) at D0, D2, D4, D8. RESULTS: The mean baseline IP values ranged between 6.55 and 31.29 mmHg in all the groups. A transient IP decrease occurred at D2 in all treated groups, and especially in the concomitant group which exhibited a significant IP reduction compared to D0. A significant decrease in both the peak intensity and the area under the curve was observed at D4 in the group with concomitant administration of both molecules which yielded maximal inhibition of the tumor volume and the number of vessels. No correlation was found between IP values and volume or perfusion parameters, indicating complex relationships between IP and vascularization. No IP gradients were found between the center and the periphery but IP values in these two regions were significantly correlated (R = 0.93). CONCLUSION: The results suggest that IP variations could be predictive of vascular changes and that one single IP measurement is sufficient to fully characterize the whole tumor.

Advanced hepatocellular carcinoma: early evaluation of response to bevacizumab therapy at dynamic contrast-enhanced US with quantification--preliminary results.

PURPOSE: To investigate whether there is any correlation between standard efficacy endpoints-specifically, tumor response, progression-free survival, and overall survival-and tumor perfusion parameters measured by using dynamic contrast material-enhanced ultrasonography (US) in patients with advanced hepatocellular carcinoma (HCC) treated with bevacizumab. MATERIALS AND METHODS: The institutional review board approved the study, and all patients provided written informed consent before their enrollment. Between June 3, 2005, and September 28, 2007, 42 patients (33 men, nine women; median age, 62 years; age range, 23-84 years) participated in this phase II study of single-agent bevacizumab treatment. Tumor response (based on RECIST [response evaluation criteria in solid tumors]) at 2 months was assessed in 37 patients, and progression-free survival and overall survival were assessed in all 42 patients. Dynamic contrast-enhanced US (ie, dynamic US) was performed before treatment (day 0); on days 3, 7, 14, and 60 after treatment; and every 2 months thereafter. Tumor perfusion parameters were estimated quantitatively from contrast material uptake curves constructed from raw linear data. The changes in dynamic US functional parameters between day 0 and the later time points were compared between treatment responders and nonresponders by using nonparametric tests. Given multiple comparisons, P < .001 indicated significance. RESULTS: The percentage decrease in several dynamic US parameters between day 0 and day 3 showed trends toward correlation with (a) tumor response in terms of total area under the time-intensity curve (AUC) (P = .02), AUC during wash in (P = .04), AUC during washout (P = .02), and time to peak intensity (P = .03); (b) progression-free survival in terms of time to peak intensity (P = .028); and (c) overall survival in terms of AUC (P = .002) and AUC during washout (P = .003). CONCLUSION: Dynamic US can be used to quantify dynamic changes in tumor vascularity as early as 3 days after bevacizumab administration in patients with HCC. These early changes in tumor perfusion may be predictive of tumor response at 2 months, progression-free survival, and overall survival, and they may be potential surrogate measures of the effectiveness of antiangiogenic therapy in patients with HCC.

Benefits of contrast-enhanced sonography for the detection of liver lesions: comparison with histologic findings.

OBJECTIVE: The objective of our study was to compare the usefulness of contrast-enhanced sonography with baseline sonography in detecting malignant liver lesions. SUBJECTS AND METHODS: This prospective study included 116 patients. All patients underwent a preoperative conventional sonography examination followed by sonography after injection of contrast agent combined with the use of perfusion software (vascular recognition imaging or pulse subtraction imaging). Histopathologic analysis was the reference standard used to compare the diagnostic value of baseline sonography versus contrast-enhanced sonography. RESULTS: Eighty-two patients underwent hepatic surgery, 31 did not because of disseminated lesions, and the remaining three patients did not meet inclusion criteria. Three hundred six surgically proven lesions were taken into account for comparison of the two techniques: 147 were detected on baseline sonography and 177 on contrast-enhanced sonography. Histopathologic analysis revealed 233 malignant and 73 benign lesions. Sensitivity and specificity were improved on contrast-enhanced sonography compared with baseline sonography for the detection of malignant lesions: 68.7% versus 58.8% and 67% versus 50.7%, respectively. Contrast-enhanced sonography detected 23 additional malignant lesions that had been seen as lacuna at the portal venous phase and characterized as 19 benign nodules, thus improving the performance of sonography in 13.7% of the cases. CONCLUSION: Contrast injection improved the sensitivity and specificity of baseline sonography and should be performed in routine practice if hepatic surgery is being considered for the management of liver lesions.

Methodology for quantifying interactions between perfusion evaluated by DCE-US and hypoxia throughout tumor growth.

The objective was to validate a combination of two new technologies to depict tumor physiology both temporally and spatially with dynamic contrast-enhanced sonography and an oximeter. Human cancer prostate tumors xenografted onto mice were followed for three weeks using dynamic contrast-enhanced ultrasonography (DCE-US) to detect tumor perfusion. Time intensity curves in linear data were quantified on four regions-of-interest (ROI, main tumor section and its anterior, central and posterior intra-tumoral areas) to extract three indices of perfusion. An oxygen sensor was guided by sonography to obtain accurate pO(2) measurements in the three predefined areas of tumors during their development. No impact on tumor growth of subsequent pO(2) probe insertion was detected. Among the four ROIs studied, the local central tumor showed significant perfusion and oxygenation variations throughout the experiment. A correlation was observed between local central tumor perfusion and pO(2), both of them decreasing through time (p = 0.0068; r = 0.66). The methodology which we developed demonstrated the potential of combining DCE-US with direct tissue pO(2) measurements, improving the description of complex intratumoral dynamic behavior.

To predict progression-free survival and overall survival in metastatic renal cancer treated with sorafenib: pilot study using dynamic contrast-enhanced Doppler ultrasound.

INTRODUCTION: The objective of this study was to evaluate dynamic contrast-enhanced Doppler ultrasound (DCE-US) with perfusion software (Vascular Recognition Imaging) and contrast agent injection as a predictor of tumour response, progression-free survival (PFS) and overall survival (OS). PATIENTS AND METHODS: Thirty patients with a metastatic renal cell carcinoma (RCC) already enrolled in a double-blind randomised study were evaluated. Examinations were performed at baseline, and after 3 and 6 weeks on sorafenib or a placebo in patients with tumour targets that were accessible to DCE-US. RESULTS: A total of 85 examinations were performed, 30 at baseline, 28 at 3 weeks and 27 at 6 weeks. The combination of a decrease in contrast uptake exceeding 10% and stability or a decrease in tumour volume allowed us to discriminate seven good responders and 20 poor responders at 3 weeks. There was a statistically significant difference in PFS (p=10(-4)) and OS (p=10(-4)) between good and poor responders. CONCLUSION: DCE-US is a new noninvasive imaging technique which might be an effective tool for evaluating antiangiogenic drugs in renal cancer.

Gastrointestinal stromal tumors treated with imatinib: monitoring response with contrast-enhanced sonography.

OBJECTIVE: The purpose of this study was to evaluate contrast-enhanced Doppler sonography with perfusion software as a predictor of early tumor response to imatinib (Glivec) in c-kit-positive gastrointestinal stromal tumors (GISTs). SUBJECTS AND METHODS: Thirty patients (59 tumors) with metastases or a recurrence from a GIST were prospectively included in a single-center imaging trial. Contrast-enhanced Doppler sonography was performed with an Aplio scanner the day before (day-1) starting oral treatment (400 mg) and at days 1, 7, 14, 60, 90, and 6 months, 9 months, and 1 year. The percentage of contrast uptake (Levovist or Sonovue) before treatment and at the different stages of follow-up was evaluated by two radiologists. Digitized quantification was performed using Photoshop software. To define the benchmark standard, all patients were rated as responders or nonresponders at 2 and 6 months by a board consisting of oncologists and radiologists who had all clinical and imaging data at their disposal. Changes in the percentage of contrast uptake at each sonographic examination were compared statistically. RESULTS: A total of 185 examinations were performed. Forty-four lesions in 24 patients were completely evaluated at 2 months, and 29 lesions in 15 patients were completely evaluated at 6 months. Initial contrast uptake at day 1 was predictive of the future response. A strong correlation was found between the decline in tumor contrast uptake at days 7 and 14 and tumor response (p < 10(-4)). CONCLUSION: Contrast-enhanced Doppler sonography is a noninvasive imaging technique that allows the early prediction of tumor response in c-kit-positive GIST treated with Glivec.

Combination of HIFU therapy with contrast-enhanced sonography for quantitative assessment of therapeutic efficiency on tumor grafted mice.

The objective was to evaluate treatment efficiency of a new high-intensity focused ultrasound (HIFU) prototype combining a therapeutic transducer with a sonographic probe. The optimal HIFU sequence was defined on ex vivo samples before in vivo evaluation of tumor ablation was performed by perfusion quantification after contrast agent injection. The original feature of this prototype is a 9-MHz sonographic probe in a HIFU device and connected to an Aplio (Toshiba) sonograph. Acoustical power and treatment time were determined on ex vivo livers to generate 1-cm-long lesions. Lesion reproducibility was assessed for the power and treatment time selected. The gap between lesions and HIFU displacement shot procedures were optimized to ablate a 1-cm3 volume. The optimized protocol was applied to five murine tumors in vivo. Tumor ablation was quantified according to (1) contrast uptake (CU) after HIFU using perfusion software (Toshiba) in "vascular recognition imaging" mode and Sonovue (Bracco) contrast agent, and (2) the percentage of necrosis quantified on histologic slides. Ex vivo results: optimized settings, at 442 W/cm2 applied during three cycles (3 s on/5 s off) generated 10 identical elementary lesions measuring 9.78 (+/-0.66) * 2.11 (+/-0.33) mm2. A 4-mm gap between adjacent lesions and a 2-min pause between shot lines were found optimal. In vivo results: 60 % (+/-22) mean reduction in CU after HIFU and tumor necrosis histologically estimated at 58 % (+/-5.7) were quantified for the five animals. The therapeutic potential of this HIFU prototype was demonstrated in vivo through objective quantification of tumor ablation based on CU.

In vitro echogenicity characterization of poly[lactide-coglycolide] (plga) microparticles and preliminary in vivo ultrasound enhancement study for ultrasound contrast agent application.

OBJECTIVES: This work includes (1) the characterization of a reproducible poly[lactide-coglycolide] (PLGA) microparticle preparation with an optimial mean diameter and size distribution and (2) the preliminary in vivo ultrasonographic investigation of PLGA microparticles. METHODS: A first series of PLGA microparticle preparations (1 to 15 mum) was acoustically characterized on a hydrodynamic device to select the most appropriate for ultrasound contrast agent application. Preparations of 3-microm microparticles were selected, characterized at different doses, and then injected into 20 melanoma grafted mice for contrast-enhanced power Doppler ultrasonography evaluation. RESULTS: The 3-microm microparticles (3.26-microm mean diameter with 0.41-microm standard deviation) led to in vitro enhancement of 18.3 dB at 0.62 mg/mL. In vivo experiments showed 47% enhancement of intratumoral vascularization detection after PLGA injection, significantly correlated (P < 0.0001) with preinjection intravascularization and tumoral volume. No toxicity was histologically observed. CONCLUSION: The 3-microm PLGA microparticles provided significant enhancement in vitro and in vivo without any toxicity.

Doppler US with perfusion software and contrast medium injection in the early evaluation of radiofrequency in breast cancer recurrences: a prospective phase II study.

INTRODUCTION: The aim of this study was to determine the efficacy of Doppler ultrasonography (US) with perfusion software and contrast agent injection (DUPC) during radiofrequency (RF) treatment of local recurrent breast cancer. MATERIALS AND METHODS: Ten patients were included in this monocentric prospective phase II study. DUPC was performed for each patient the day before treatment and immediately after RF in the operating suite. RF ablation was followed by a total mastectomy. The results of DUPC were compared to the histologic analysis of the operative specimen. RESULTS: Before RF, contrast uptake exceeded 70% in 5 lesions and was less than 50% in 5 lesions. Immediately after RF, no vascularization was detected with DUPC in 9 of the 10 lesions. Contrast uptake attaining 30% was depicted in the remaining lesion. At histologic analysis, complete tumour destruction was confirmed in 7 of the 10 operative specimens. CONCLUSION: In this study, DUPC is highly efficient and better adapted for the confirmation of tumour destruction in tumours that are hypervascularised before RF compared to hypovascularised lesions.

Effects of single-dose injectable paracetamolversus propacetamol in pain management after minor gynecologic surgery: A multicenter, randomized, double-blind, active-controlled, two-parallel-group study.

BACKGROUND: Intravenous administration is the route of choice for drug therapy in the immediate postoperative period. Propacetamol (ProAPAP), an injectable prodrug of paracetamol requiring reconstitution, has demonstrated efficacy in managing acute pain and fever. However, it has been associated with pain at the injection site. A stable, ready-to-use formulation of paracetamol solution infused intravenously (IV-APAP) has been developed and might be associated with less pain at the injection site compared with ProAPAR. OBJECTIVE: The objective of this study was to assess the tolerability and efficacy of a single dose of IV APAP 1 g compared with those of a single dose of ProAPAP 2 g in patients with moderate to severe pain after minor gynecologic surgery. METHODS: This single-dose, randomized, double-blind, active-controlled,2-parallel-group study was conducted at 23 hospitals and outpatient clinics in France. After minor gynecologic surgery, patients reporting moderate to severe pain were randomized to receive a single 15-minute infusion of IV-APAP 1 g or ProAPAP 2 g (bioeyuivalent doses). Tolerability was monitored using local and systemic adverse event (AE) reporting, clinical examination including vital sign measurement, and patients' ratings of acceptability of the infusion. Efficacy end points included pain intensity at 0, 1, 2, 4, and 6 hours; median time to rescue medication (defined as the time at which 50% of patients requested rescue medication); and percentage of patients requesting rescue medication. Patients' satisfaction with the study drugs was assessed using patient's global evaluation (PGE) and the percentage of patients willing to receive the treatment again. RESULTS: Of the 163 women who were randomized, 161 received the studymedication. The IV-APAP group comprised 80 patients (mean [SD] age, 38.3 [12.8] years [range, 18.0-69.0 years]; mean [SD] weight, 61.1 [11.0] kg [range, 49.0-90.0 kg]), and the ProAPAP group comprised 81 patients (mean [SD] age, 33.9 [12.0] years [range, 18.0-67.0 years]; mean [SD] weight, 61.6 [10.2] kg [range, 42.0-95.5 kg]); the difference in mean age between the 2 groups was statistically significant (P < 0.05). The incidence of local treatment-emergent AEs (TEAEs) was significantly lower in the IV-APAP group compared with that in the ProAPAP group (7.5% vs 38.3%; P < 0.001). No between-group differences in the incidence of systemic TEAEs was found. All patients in the IV-APAP group found the infusion tolerable, compared with 95% of patients in the ProAPAP group. The median time to rescue medication was not evaluated because <50% of the patients in each group requested it. No significant differences in mean pain intensity score or percentage of patients requesting rescue medication were found between the 2 groups at any time point. The percentages of patients in the IV-APAP and ProAPAP groups who rated the study medication as good or excellent on the PGE (83.6% vs 75.6%; P < 0.05) and who were willing to receive the same treatment again (96.0% vs 81.0%; P = 0.005) were significantly higher with IV-APAP compared with ProAPAP. CONCLUSION: In these patients with moderate to severe pain after minor gynecologic surgery, a single dose of IV-APAP was associated with better local tolerability, similar analgesic efficacy, and greater patient satisfaction compared with a single bioequivalent dose of ProAPAP.

Validation of a new method for quantifying in vivo murine tumor necrosis by sonography.

RATIONALE AND OBJECTIVES: At present, the gold standard to evaluate tumor necrosis is histology. We described here a new method to quantify the degree of tumor necrosis by ultrasonography. This technique combines ultrasound exploration of tissue and post-treatment of the numerical sequences using a dedicated software to evaluate backscattered power within the tumor. MATERIALS AND METHODS: In order to establish that the backscattered power could be considered as a relevant marker of tumor necrosis, we performed (1) intra- and interoperator reproducibility in estimation of tumor dimensions obtained on sonographic scans; and (2) intra- and interoperator reproducibility in quantification of backscattered power in postprocessing using the HDILab software. The third part of the study consisted of correlating the degree of tumor necrosis estimated by histology and the ultrasound backscattered power, both obtained on xenografted melanomas at different days after tumor transplantation. RESULTS: Results concerning tumor size estimations and quantification of echogenicity were reproducible (coefficient of variation < 4.33%). The degree of necrosis measured in histology and echogenicity were significantly negatively correlated (P < 0.003). CONCLUSION: In conclusion, backscattered power could be considered as a relevant parameter to quantify tumor necrosis in vivo.

Preoperative selective portal vein embolization before hepatectomy for liver metastases: long-term results and impact on survival.

BACKGROUND: Some patients cannot undergo curative surgical procedures for liver metastases because of the risk of severe postoperative hepatic failure, which stems from a too-small future remaining liver (FRL). Preoperative portal vein embolization (PVE) is an effective means of creating hypertrophy of the FRL, thus permitting safe hepatic resection. The aim of this retrospective study was to investigate the long-term results of this technique. METHODS: Sixty-eight patients underwent PVE. Of those, 60 (88%) subsequently underwent hepatic resection. Indication for PVE was an estimated FRL ratio (assessed by volumetric computed tomography) of less than 30%. However, if the patient had undergone multiple courses of chemotherapy, the threshold was 40%. The origin of the primary neoplasm was colorectal in 41 patients (68%); in the remaining 19 (32%), the primary neoplasms originated at other sites. RESULTS: Mean growth of the estimated FRL measured by computed tomography 1 month after PVE was 13%. Major complications after hepatectomy occurred in 27% of the patients, and the operative mortality rate was 3%. For the 60 patients who underwent PVE followed by hepatic resection, the 5-year overall survival rate and the disease-free survival rate were 34% and 24%, respectively. The 5-year overall survival rate and the disease-free survival rate of patients with colorectal metastases only were 37% and 21%, respectively. CONCLUSIONS: The long-term survival rate after PVE followed by resection is comparable with the survival rate obtained after resection without preoperative PVE. The 5-year survival rate of patients undergoing PVE followed by hepatectomy justifies the use of this technique. This technique thus increases the suitability of resection as a treatment choice for patients with liver metastases. PVE should number among the therapeutic options available to every hepatic surgeon.

High-frequency sonography and color Doppler in the management of pigmented skin lesions.

We aimed to evaluate high-frequency sonography (HFS) coupled with color Doppler in the management of pigmented skin lesions (PSL). HFS examination was performed in 111 patients with 130 PSL. A color Doppler study was conducted in 107 lesions, to assess intralesional vascularization. Imaging findings were compared with histologic diagnosis. In the case of melanoma, sonographic and histologic maximum thickness measurements were compared. HFS showed 114 of the 130 lesions. Among the detected lesions, HFS alone provided 100% sensitivity and 100% specificity in the distinction of melanoma/nevi from other lesions, and 100% sensitivity and 32% specificity in the distinction of melanomas from nonmelanoma lesions. Sonographic and histologic measurement of melanoma thickness strongly correlated (r > 0.96, p < 0.001). Color Doppler detection of intralesional vessels had a 100% specificity and 34% sensitivity in the distinction of melanomas from other PSL. HFS coupled with color Doppler is a simple, reliable tool for PSL management.

Simultaneous percutaneous right portal vein embolization and left liver tumor radiofrequency ablation prior to a major right hepatic resection for bilateral colorectal metastases.

BACKGROUND/AIMS: Hepatic resection offers the best chance of survival for patients with liver metastases (LM) of colorectal origin. However, some patients are not eligible for surgery because of a too small future liver remnant (FLR) which carries a high risk of severe postoperative liver failure. The operability status of these patients can be favorably changed by selective right portal vein embolization (PVE) which induces compensatory growth of the left liver. However, during liver regeneration following right PVE, the left LM growth rate is faster than that of the non-embolized normal liver parenchyma. This study aimed at examining an approach for those patients in which there is bilateral LM potentially resectable following portal vein embolization, but in which there is a risk of rapid liver metastasis growth in the non-embolized liver. METHODOLOGY: Between October 1998 and January 2001, 5 patients underwent simultaneous right PVE and radiofrequency ablation (RFA) of a left LM, prior to a major right-sided hepatectomy for initially unresectable bilateral LM. All these patients had one LM in the left liver in addition with multiple LM in the right liver. Simultaneous right PVE and left RFA was performed percutaneously under intravenous sedation and analgesia. One month later, hepatectomy was undertaken. To allow histologic assessment of the RFA effectiveness, the previously treated left-sided tumor was also resected and analyzed. RESULTS: Simultaneous PVE-RFA was successful in all patients. No tumor growth on the RFA site was observed during the interval between PVE-RFA and surgery. Histologic examination showed complete tumor sterilization of the RFA necrotic zone. In the postoperative course, 1 patient died of acute liver failure. For the 4 remaining patients, morbidity was minimal (transient bile leak in one patient). CONCLUSIONS: Simultaneous percutaneous right PVE and left RFA is feasible. This procedure allowed good left-sided tumor control during liver growth following PVE in all five patients. It is the most logical procedure for patients with bilateral colorectal LM needing right PVE before resection, if the left concomitant LM is small and accessible to percutaneous RFA. This procedure should be preferred because it eliminates the risk of left LM growth during the 1-month interval between PVE and surgery.

[Locoregional therapy of neuroendocrine tumors]. / Traitements loco-régionaux des tumeurs neuro-endocrines.

In digestive neuroendocrine tumours, surgery is the cornerstone of the treatment of the primary tumour. The diameter of the lesion is the main prognostic indicator and consequently impacts the extent of the resection. Types of resection, regarding to tumours sizes and locations, are reported. In metastatic forms, an aggressive policy of multidisciplinary treatments is proposed. Arterial chemoembolization is very efficient in controlling clinical symptoms and liver tumours progression, and allows secondary radical resections in selected cases. Chemoembolization is actually considered as the first line treatment in well-differentiated forms, with rapid progression.

Dynamic contrast-enhanced ultrasonography (DCE-US) and anti-angiogenic treatments.

Dynamic contrast-enhanced ultrasonography (DCE-US) is a current functional imaging technique enabling a quantitative assessment of tumor perfusion using raw linear data. DCE-US allows calculating several parameters as slope of wash-in or area under the curve representing, respectively, blood flow or blood volume. Decrease of vascularization can easily be detected in responders after 1 or 2 weeks of anti-angiogenic treatment for gastrointestinal stromal tumors (GIST), renal cell carcinoma (RCC), and hepatocellular carcinoma (HCC) and is correlated with progression-free survival and overall survival in RCC or HCC. DCE-US is supported by the French National Cancer Institute (INCa), which is currently studying the technique in metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors and renal cell carcinoma, as well as in primary hepatocellular carcinoma, to establish the optimal perfusion parameters and timing for quantitative anticancer efficacy assessments. Currently 479 patients are included in 19 centers and the preliminary results on 400 patients with 1096 DCE-US demonstrated that the area under the curve (AUC) quantified at 1 month could be a robust parameter to predict response at 6 months.

Estimation of intra-operator variability in perfusion parameter measurements using DCE-US.

AIM: To investigate intra-operator variability of semi-quantitative perfusion parameters using dynamic contrast-enhanced ultrasonography (DCE-US), following bolus injections of SonoVue(®). METHODS: The in vitro experiments were conducted using three in-house sets up based on pumping a fluid through a phantom placed in a water tank. In the in vivo experiments, B16F10 melanoma cells were xenografted to five nude mice. Both in vitro and in vivo, images were acquired following bolus injections of the ultrasound contrast agent SonoVue(®) (Bracco, Milan, Italy) and using a Toshiba Aplio(®) ultrasound scanner connected to a 2.9-5.8 MHz linear transducer (PZT, PLT 604AT probe) (Toshiba, Japan) allowing harmonic imaging ("Vascular Recognition Imaging") involving linear raw data. A mathematical model based on the dye-dilution theory was developed by the Gustave Roussy Institute, Villejuif, France and used to evaluate seven perfusion parameters from time-intensity curves. Intra-operator variability analyses were based on determining perfusion parameter coefficients of variation (CV). RESULTS: In vitro, different volumes of SonoVue(®) were tested with the three phantoms: intra-operator variability was found to range from 2.33% to 23.72%. In vivo, experiments were performed on tumor tissues and perfusion parameters exhibited values ranging from 1.48% to 29.97%. In addition, the area under the curve (AUC) and the area under the wash-out (AUWO) were two of the parameters of great interest since throughout in vitro and in vivo experiments their variability was lower than 15.79%. CONCLUSION: AUC and AUWO appear to be the most reliable parameters for assessing tumor perfusion using DCE-US as they exhibited the lowest CV values.

Dynamic contrast-enhanced ultrasonography (DCE-US): a new tool for the early evaluation of antiangiogenic treatment.

Dynamic contrast-enhanced ultrasonography (DCE-US) is a new functional technique enabling a quantitative assessment of solid tumor perfusion using raw linear data. DCE-US allows the calculation of parameters as slope of wash-in or area under the curve (AUC) representing, respectively, blood flow or blood volume. Reduction in tumor vascularization can easily be detected in responders after 1 or 2 weeks and is correlated with progression-free survival and overall survival in renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC). DCE-US is supported by the French National Cancer Institute (INCa), which is currently studying the technique in metastatic breast cancer, melanoma, colon cancer, gastrointestinal stromal tumors and renal cell carcinoma, as well as in primary hepatocellular carcinoma, to establish the optimal perfusion parameters and timing for quantitative anticancer efficacy assessments. Currently 490 patients are included in 20 centers and the preliminary results on 400 patients with 1,096 DCE-US demonstrated that AUC could be a robust parameter to predict response.

Metastatic renal cell carcinoma treated with sunitinib: early evaluation of treatment response using dynamic contrast-enhanced ultrasonography.

PURPOSE: To determine the utility of dynamic contrast-enhanced ultrasonography (DCE-US) as a prognostic tool for metastatic renal cell carcinoma patients receiving sunitinib and to identify DCE-US parameters that correlate with early treatment response. EXPERIMENTAL DESIGN: Thirty-eight patients received 50 mg/d sunitinib on schedule 4/2 (4 weeks on followed by 2 weeks off treatment). After two cycles, response evaluation criteria in solid tumors were used to classify patients as responders or nonresponders. DCE-US evaluations were done before treatment and at day 15; variations between days 0 and 15 were calculated for seven DCE-US functional parameters and were compared for responders and nonresponders. The correlation between DCE-US parameters and disease-free survival (DFS) and overall survival (OS) was assessed. RESULTS: The ratio between DCE-US examinations at baseline and day 15 significantly correlated with response in five of the seven DCE-US parameters. Two DCE-US parameters (time to peak intensity and slope of the wash-in) were significantly associated with DFS; time to peak intensity was also significantly associated with OS. CONCLUSIONS: DCE-US is a useful tool for predicting the early efficacy of sunitinib in metastatic renal cell carcinoma patients. Robust correlations were observed between functional parameters and classic assessments, including DFS and OS.

[Liver chemoembolization: an update]. / Le point sur la chimioembolisation hépatique.

Percutaneous intraarterial techniques for treatment of liver tumors are continuously under development. New therapeutic methods are available (such as microsphere-encapsulated chemotherapy or yttrium 90 microspheres) and presently under evaluation. These methods enlarge the field of indications, i.e. in metastasis from colorectal cancer. Hepatocellular carcinoma and metastasis from neuroendocrine tumours are the main pathologies favourably responding to "conventional" chemoembolization. Thank to controlled studies and meta-analysis performed along the last ten years, curative-palliative-as well as adjuvant-indications for chemoembolization in hepatocellular carcinoma are now wellestablished.