Alain Roche

A randomized trial of hepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma

A randomized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma. These patients represented 41% of patients with hepatocellular carcinoma seen during the inclusion period. In the remaining 59%, 9% had resectable tumours and 50% had unresectable tumours with contraindication for chemoembolization. Patients received either repeated chemoembolization with gelfoam powder and doxorubicin (group 1) or symptomatic treatment (group 2). There was no difference in age, prevalence of cirrhosis or staging according to Okuda between the two groups of patients. A complete tumour response (assessed by arteriography, ultrasonography and serum alphafetoprotein) was observed in four patients, and a partial response in three other patients from group 1. Actuarial survival rates were 33 and 24% in group 1 and 52 and 31% in group 2 at 6 and 12 months, respectively (differences were not significant--logrank test). With the treatment used in our study, chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma. There were, however, some complete or partial responses. The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients. Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma.

Treatment of unresectable hepatocellular carcinoma with lipiodol chemoembolization: a multicenter randomized trial

BACKGROUND/AIMS Lipiodol chemoembolization is a widely used method of treatment in patients with unresectable hepatocellular carcinoma, but its efficacy is still debated. The aim of our study was to assess the efficacy of lipiodol chemoembolization in patients with unresectable hepatocellular carcinoma. METHODS Seventy-three patients with unresectable hepatocellular carcinoma, but without severe liver disease or portal vein occlusion, were randomly assigned to receive either repeated lipiodol chemoembolization (lipiodol, cisplatin (2 mg/kg), lecithin, and gelatin sponge injected into the hepatic artery) plus tamoxifen (40 mg) or tamoxifen alone. The main end-point was survival. RESULTS The 37 patients in the lipiodol chemoembolization group received 104 courses (median 3 per patient). By 1 September 1996, 58 patients had died: 30 in the lipiodol chemoembolization group and 28 in the tamoxifen group. There was no difference in survival between the two groups (p=0.77). The relative risk of death in the lipiodol chemoembolization plus tamoxifen group as compared to the tamoxifen group was 0.92 (95% confidence interval 0.55 to 1.56). At 1 year, survival was 51% and 55%, respectively. An objective tumoral response was more frequently observed in the lipiodol chemoembolization group than in the tamoxifen group (24 versus 5.5%, respectively, p=0.046). Lipiodol chemoembolization caused two deaths and induced signs of liver failure in 51% of the patients assigned to this treatment. CONCLUSION In our randomized study, lipiodol chemoembolization did not improve the survival of patients with unresectable hepatocellular carcinoma treated with tamoxifen.

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.

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.

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. Clin Cancer Res; 16(4); 1216–25

Radio Frequency Ablation of Renal Cell Carcinoma: Preliminary Clinical Experience

PURPOSE We assess the feasibility, safety and efficacy of radio frequency ablation of small peripheral renal cell carcinomas. MATERIALS AND METHODS Five patients with a histologically proven renal cell carcinoma 30 to 40 mm. in diameter were treated with radio frequency ablation. A triple needle electrode was percutaneously advanced into each tumor under sonographic (4 cases) or computerized tomography (CT) (1) guidance. The radio frequency generator was activated for 15 minutes in each location where the electrode had been placed. Patients were then followed with CT and blood tests every 2 months for 6 months and every 3 months thereafter. RESULTS Four tumors required 1 radio frequency delivery and 1 required 2 applications during the same session. No complications were encountered except for a subcapsular hematoma in 1 patient, which resolved spontaneously. Two patients experienced transient hematuria. Of the patients 4 were discharged from the hospital after 2 days and 1 after 1 day. After 6 to 18 months (median 9) all patients were tumor-free on CT without suppress additional treatment. CONCLUSIONS In this small preliminary study radio frequency ablation of small peripheral renal cell carcinomas appears to be a feasible, safe and promising technique.

Malignant Gastroduodenal Obstruction: Palliation with Self-expanding Metallic Stents

PURPOSE To evaluate the feasibility, efficacy, and tolerance of self-expanding metallic stent insertion under fluoroscopic guidance for palliation of symptoms related to malignant gastroduodenal obstruction. MATERIALS AND METHODS Seventy-two patients (38 men, 34 women) aged 25-98 years (mean, 62 years) with duodenal (n = 43), antropyloric (n = 13), surgical gastrojejunostomy (n = 10), or pyloroduodenal (n = 6) malignant obstruction were referred for insertion of self-expanding metallic stents over a 6-year period. Stent insertion was performed with use of a peroral or transgastric approach when necessary (n = 11). RESULTS Stents were successfully inserted in 70 of the 72 patients (97%) and provided symptom relief in 65 patients (90%). Inserted stents were mainly uncovered vascular (n = 55) or enteral (n = 10) Wallstents. One hundred eight stents were initially inserted: one, two, three, or four stents were indicated in 43, 17, nine, and one patient, respectively. Mean follow-up was 119 days (range, 4-513 days). Mean stent patency was 113 days (range, 4-513 days). Mean survival of patients was 120 days. During follow-up, stent obstruction occurred in seven patients as a result of tumoral overgrowth (n = 5) or ingrowth (n = 2). Complications occurred in 12 of the 72 patients (17%), including stent migration (n = 8), stent fracture (n = 1), duodenal perforation (n = 1), and death related to general anesthesia (n = 1). CONCLUSION Despite a significant complication rate, self-expanding metallic stent insertion under fluoroscopic guidance appears to be a feasible and useful technique in the palliative management of malignant gastroduodenal obstruction.

MRI of liver metastases from colorectal cancer vs. CT during arterial portography.

A prospective study was performed to compare, with a lesion-by-lesion analysis, the sensitivities of high field strength MRI and CT during arterial portography (CTAP) in detecting hepatic metastases from colorectal cancer. Twenty-one patients with liver metastases from colorectal cancer were prospectively investigated by high field strength MRI (1.5 or 2 T) and CTAP. High field strength MRI was performed with pre and post gadopentetate dimeglumine enhanced T1-weighted SE sequences and T2-weighted SE sequences. All patients underwent partial hepatectomy and 37 metastases were surgically and pathologically proved. The metastasis detection rate (sensitivity) was 94% (35 of 37) for CTAP and 78% (29 of 37) for high field strength MRI. The 16% (95% confidence interval: 1–31%) difference in sensitivity between CTAP and high field strength MRI was statistically significant (p < 0.05, Mc-Nemar test). The use of gadopentetate dimeglumine did not improve the sensitivity of T1-weighted SE sequences. Since our study demonstrated significant difference in sensitivities between high field strength MRI and CTAP in our group of patients, we can conclude that high field strength MRI cannot replace CTAP in the preoperative evaluation of patients with liver metastases from colorectal cancer. Computed tomography during arterial portography must be considered as the preoperative gold standard. Index Terms: Liver, neoplasms—Portography—Magnetic resonance imaging, techniques.

Epithelioid hemangioendothelioma of the liver: MR and CT findings.

The MR imaging features in five patients with hepatic epithelioid hemangioendothelioma (EHE) were correlated with CT and pathologic findings. Two hemangioendotheliomas appeared as multiple nodular lesions with a predominantly peripheral location in the liver. In three more extensive cases, the tumors formed confluent peripheral lesions with macroscopic invasion of portal or hepatic veins (n = 3), signs of portal hypertension (n = 3), and nodular hypertrophy of uninvolved liver (n = 2). These findings, suggestive of EHE, were well demonstrated by MR imaging and CT. The internal architecture of the tumors was clearly depicted on T2-weighted MR images. Viable tumor peripheries appeared moderately hyperintense relative to liver. The center of the tumors consisted of one or several concentric zones. Hyperintense central zones were composed of loose, edematous connective tissue. Hypointense zones contained mainly coagulation necrosis, calcifications, and scattered hemorrhages. Except for the presence of calcifications, the internal architecture of EHE was better defined by MR imaging than by CT.

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.