J. Leclère

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.

Evaluation of contrast-enhanced color Doppler ultrasound for the quantification of angiogenesis in vivo.

Lassau N, Koscielny S, Opolon P, et al. Evaluation of contrast-enhanced color Doppler ultrasound for the quantification of angiogenesis in vivo. Invest Radiol 2001;36:50–55. rationale and objectives.To evaluate contrast-enhanced color Doppler ultrasonography (CDUS) aimed at quantifying angiogenesis in vivo. methods.Eight colon tumors xenografted into mice were studied with CDUS both without and after injection of SHU 508A. The number of intratumor vessels and pedicles visualized with CDUS and the value of the acoustic intensity quantified by computer were compared with the evaluation of angiogenesis by study of digitized histological slides. results.SHU 508A increased the number of intratumor vessels and pedicles depicted by CDUS, which could also be quantified by acoustic intensity. The comparison of CDUS and digitized histological slide studies showed that the detection threshold after SHU 508A administration allowed visualization of small vessels (40 &mgr;m in diameter). The “hot spots” seen on histology were superimposable onto vessels seen with CDUS. Regions in which no vessels were detected by CDUS corresponded to regions in which vascularization was absent by histological analysis. conclusion.Injection of SHU 508A significantly increased vessel detection with CDUS.

Prognostic value of angiogenesis evaluated with high-frequency and colour Doppler sonography for preoperative assessment of primary cutaneous melanomas: correlation with recurrence after a 5 year follow-up period.

Objective: To study the value of high-frequency sonography (HFS) and colour Doppler sonography (CDS) in evaluating the 5 year metastatic potential of primary cutaneous melanomas (CM). Materials and methods: 111 CM were studied before surgical resection and 107 were depicted on HFS. The maximal HFS thickness was measured and compared with the Breslow thickness. A CDS study was performed in each tumour. Results: HFS thickness ranged from 0.26 to 8.0 mm and Breslow thickness from 0.15 to 8.0 mm. HFS and Breslow thickness correlated strongly (r>0.93). Intratumour vessels were depicted in 43 of the 107 CM, of which 40 were thicker than 2 mm. The median follow-up was 61 months and 27 patients developed relapses. In the univariate analyses, neovascularization visualized with CDS, sonographic thickness and the Breslow thickness were significantly linked to relapses (p<0.0001), as were lymph node status and ulceration (p=0.007 and 0.004). Conclusion: Vascularization was observed mainly in thick primary melanoma. A median follow-up of 5 years showed the prognostic value of angiogenesis evaluated by CDS.

New Hemodynamic Approach to Angiogenesis: Color and Pulsed Doppler Ultrasonography

RATIONALE AND OBJECTIVES To determine the capacity of color and spectral Doppler ultrasonography (US) to quantify angiogenesis in vivo and to characterize low-resistance intratumor blood flow. METHODS Thirty-two tumors, xenografted into mice, were studied with Doppler US. The number of intratumor vessels visualized with color Doppler US was compared with the density of microvessels and the number of vessels >100 microm determined by histologic examination. The resistance index and the peak systolic velocities were evaluated. RESULTS The number of intratumor vessels visualized by color Doppler US was correlated with the number of vessels >100 microm (P<0.001) determined histologically. When vessel density was >30, intratumor vessels were always detected by color Dopper US. The resistance index and peak systolic velocities were significantly lower in intratumor than in peritumor vessels. CONCLUSIONS Color Doppler US evaluated tumor angiogenesis accurately. Spectral analysis confirmed the low resistance of intratumor blood flow.

Prognostic value of doppler-ultrasonography in hepatic veno-occlusive disease: A study of 71 children

Background. Currently, the severity of veno-occlusive disease (VOD) is graded retrospectively on the basis of the evolution of clinical and biological criteria. The objective of this study was to describe a noninvasive method capable of predicting the severity of this disease at the time of the diagnosis. Methods. Seventy-one children who developed VOD after intensive myeloablative therapy with busulfan before hematopoietic stem cell transplantation were included in this study. Sixty-four patients underwent baseline ultrasonography (US) and Doppler examination before transplantation. All patients had posttransplantation US and Doppler examinations at the time of the clinical and biological diagnosis of VOD. Seven US morphological criteria and seven Doppler criteria were studied that yielded three individual scores: a US score, a Doppler score, and a total Doppler ultrasonography (DUS) score. Results. In the univariate analysis, three of 7 US criteria, three of 7 Doppler criteria, and the three scores were correlated with the severity of VOD after transplantation and at the time of the diagnosis. In the multivariate analysis, two US criteria (splenomegaly and ascites) and one Doppler criterion (flow recorded in para-umbilical vein) were correlated with the severity of VOD. The multivariate analysis of the pooled US and Doppler criteria showed that the flow recorded in the para-umbilical vein was the only criterion significantly associated with the grade of VOD (P =0.0001). All patients with a US-Doppler score >9 developed grade 2 or 3 VOD. Conclusion. Postgraft US and Doppler examinations have a prognostic significance according to the grade of VOD.

Évaluation fonctionnelle et précoce des traitements en cancérologie : intérêt des produits de contraste ultrasonores

Resume L’evaluation precoce et fonctionnelle des nouveaux traitements en cancerologie represente un enjeu majeur. Actuellement, les progres technologiques en echographie-Doppler permettent d’etudier la microvascularisation des tumeurs superficielles et profondes afin d’evaluer l’efficacite des nouvelles therapeutiques: 1) visant a bloquer l’angiogenese tumorale (Neovastat, Sugen, TNFα…) ou 2)detruisant physiquement la vascularisation des lesions hepatiques par radiofrequence. Il est possible de mettre en evidence des flux lents dans des microvaisseaux tumoraux et de predire l’efficacite therapeutique en fonction de la modification de cette microvascularisation avant meme qu’il n’y ait une modification du volume tumoral.L’injection de produits de contraste renforce l’efficacite de la technique et le developpement de logiciels de perfusion optimise cette detection.

Chest computed tomography (CT) in patients with micronodular lung metastases of differentiated thyroid carcinoma

Forty thoracic CT scans have been performed on 27 patients with micronodular lung metastases of differentiated thyroid carcinoma. Lung nodules were visualized in 14 out of 19 patients (78%) with functioning lung metastases, although their chest X rays were normal. However, only a small number of peripheral micronodules can be visualized by CT scan since the central micronodules remain undistinguishable from adjacent vessel structures. A close relationship has been found between the number of micronodules and the thyroglobulin (Tg) serum level. In patients previously treated by 131I for proven lung metastases and who had no uptake for several years, but in whom Tg remained detectable in the serum, CT scans have shown micronodules in 7 of the 13 patients with normal chest X rays. The present data suggest that these nodules are mainly a result of fibrosis. CT scanning appears to be an important complementary tool with regard to 131I whole body scintigraphies in the radiologic diagnosis of lung nodules and in the assessment of radioiodine therapy.

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.

Dialogue entre le radiologue et le patient atteint d’un cancer

Resume Avec les progres de la medecine et l’evolution de notre societe, on assiste a une augmentation du nombre de patients atteints de cancer et a un changement dans les relations medecin-malade. Les droits des malades sont desormais inscrits dans la Charte du Patient Hospitalise, la loi Huriet et la loi du 4 mars 2002. L’evolution des maladies cancereuses est ponctuee de nombreux examens d’imagerie et le radiologue est alors en premiere ligne. C’est souvent lui qui decouvre les anomalies et qui doit trouver les premiers mots. La tache est d’autant plus difficile qu’il n’a recu aucune formation specifique pour la gestion de situations difficiles telles que l’annonce d’une mauvaise nouvelle. Le risque est grand d’attitudes inadaptees, de mots maladroits qui marqueront negativement l’esprit des malades. Meme si nous avons le desir et la sensation de bien faire, nous pouvons tirer de grands benefices d’une reflexion sur nos modalites relationnelles pour les ameliorer et mieux repondre a la plus grande demande d’information des malades. Le radiologue doit savoir faire mais la technique n’est pas suffisante, il doit aussi savoir dire, ni trop ni trop peu et il doit savoir etre en s’appuyant sur sa competence clinique, ses qualites relationnelles avec les malades et le respect de leur volonte et de leurs droits.

Improving the interpretation of bone marrow imaging in cancer patients.

Magnetic resonance imaging (MRI) is the best technique for bone marrow imaging. The MRI signal of bone marrow depends on the quantity of fat it contains and on its cellularity. Evaluation of marrow of patients treated for cancer is complicated by age and osseous site related changes in the distribution of normal haematopoietic (red) and fatty (yellow) marrow and by the changes induced by treatments: decrease in pathological cellularity, increase in fat proportion, conversion of red marrow to fatty marrow or, conversely, reconversion of fatty marrow in normal haematopoietic red marrow. The treatments used in oncology modify pathological marrow but also normal marrow and may sometimes lead to complications. These modifications may be focal or diffuse, homogeneous or patchy and symmetrical or asymmetric. The knowledge of bone marrow physiological status and post-therapeutic patterns is important for the interpretation of marrow disorders and effects of therapy and to avoid false-positive diagnosis of marrow metastases and tumour progression. The aim of this paper is to recall the MRI patterns of normal bone marrow and normal variations and to show the effects of treatments on bone tissue and normal bone marrow and treatment-related modifications on pathological marrow.