Validation of a New Method for Quantifying In Vivo Murine Tumor Necrosis by Sonography

Rouffiac, Valérie; Bouquet, Céline; Lassau, Nathalie; Opolon, Paule; Koscielny, Serge; Péronneau, P.; Perricaudet, Michel; Roche, Alain

doi:10.1097/01.rli.0000124457.99229.bb

Cited by 30 publications

(17 citation statements)

References 16 publications

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“…21 More recently, the link between the echogenecity and the degree of intra-tumoral necrosis was evaluated in a preclinical study. 22 In this study, we decided to investigate the relative antiangiogenic and antitumor properties of antiangiogenic inhibitors, using contrast-enhanced HFCDUS. We investigated and validated the potential clinical usefulness of contrast-enhanced HFCDUS/HFUS in assessing dynamically the effects of the previously studied angiogenesis inhibitors, Canstatin 14 and K1-5, 23 over a treatment period of 6 weeks, using IHC as the reference standard.…”

Section: Introductionmentioning

confidence: 99%

Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration

et al. 2006

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Tumor growth is dependent both on endothelial and tumor cells. The aim of this study was to investigate dynamically whether changes in tumor vasculature implicate tumor tissue degeneration during antiangiogenic therapies. In order to quantify intra-tumor vascularization and necrosis, we have used ultrasound technology. This study has identified essential parameters needed to quantify specifically and sensitively the number of microvessels and the extent of necrosis in xenografted human carcinomas during natural tumor evolution, using contrast-enhanced high-frequency ultrasonography with (HFCDUS) or without (HFUS) color Doppler. We showed that quantification of intra-tumor microvessels between HFCDUS and immunohistochemistry is correlated using an anti-CD31 antibody. Furthermore, quantification of tumor necrosis with HFUS was confirmed by histological examination of hematoxylin-eosin-saffraninstained sections over the observation period. Subsequently, for the assessment of novel angiogenic inhibitors, HFCDUS and HFUS were used to elucidate the underlying dynamics linking vessel inhibition and tumor eradication. We describe a novel application for HFCDUS/HFUS that constitutes an effective, convenient, and non-invasive method for clinical assessment of angiogenic inhibitors. In conclusion, we showed that tumor cells abruptly became necrotic following an antivascular therapy, whereas untreated tumors were protected from degeneration by a significant blood supply.

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Section: Introductionmentioning

confidence: 99%

Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration

et al. 2006

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“…One of the major advantages of DCE-US for the evaluation of new antitumor treatments is that the cost of the examination is low (70 per vial of contrast agent) and it can be repeated without adverse effects. In addition, it has been previously shown that this technique is not operator dependent (22). Recent developments, such as the use of raw linear data and perfusion and quantification software, have improved the accuracy and sensitivity of DCE-US.…”

Section: Discussionmentioning

confidence: 99%

Metastatic Renal Cell Carcinoma Treated with Sunitinib: Early Evaluation of Treatment Response Using Dynamic Contrast-Enhanced Ultrasonography

Lassau

Koscielny

Albigès

et al. 2010

Clinical Cancer Research

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170

116

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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. ©2010 AACR.

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“…24 Sunitinib induces endothelialcell apoptosis in vitro and in animal-tumour models, and pathologic changes observed suggest that dermal-vessel alteration and apoptosis might be due to direct anti-VEGFR or anti-PDGFR effects of sunitinib on dermal endothelial cells. 27 Sunitinib therapy for metastatic RCC Management strategies § for hand-foot syndrome (palmar-plantar erythrodysesthesia syndrome) include having a manicure and pedicure before treatment as a preventative measure, treatment interruptions and a shorter course (2 weeks) of therapy much more often than dose reduction. Palliative intervention includes moisturizers, foot and hand care products (e.g., gel pad inserts, cotton gloves and clobetasol propionate cream), and medication for pain management.…”

Section: Hand-foot Syndrome or Acral Erythemamentioning

confidence: 99%

Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects

Kollmannsberger

Soulières

Wong

et al. 2012

CUAJ

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Sunitinib, a new vascular endothelial growth factor receptor inhibitor, has demonstrated high activity in renal cell carcinoma (RCC) and is now widelyused for patients with metastatic disease. Although generally well tolerated andassociated with a low incidence of common toxicity criteria grade 3 or 4 toxicities, sunitinib exhibits a distinct pattern of novel side effects that require monitoring and management. This article summarizes the most important side effects and proposes recommendations for their monitoring, prevention and treatment,based on the existing literature and on suggestions made by an expert groupof Canadian oncologists. Fatigue, diarrhea, anorexia, oral changes, skin toxicityand hypertension seem to be the most clinically relevant toxicities of sunitinib. Fatigue may be partly related to the development of hypothyroidismduring sunitinib therapy for which patients should be observed and, if necessary, treated. Hypertension can be treated with standard antihypertensivetherapy and rarely requires treatment discontinuation. Neutropenia and thrombocytopenia usually do not require intervention, in particular no episodes ofneutropenic fever have been reported to date. A decrease in left ventricula rejection fraction is a rare, but potentially life-threatening side effect. Becauseof its metabolism by cytochrome P450 3A4 a number of drugs can potentiallyinteract with sunitinib. Clinical response and toxicity should be carefullyobserved when sunitinib is combined with either a cytochrome P450 3A4 induceror inhibitor and doses adjusted as necessary. Knowledge about side effects, as well as the proactive assessment and consistent management of sunitinib related side effects, is critical to ensure optimal benefit from sunitinib treatment.

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Validation of a New Method for Quantifying In Vivo Murine Tumor Necrosis by Sonography

Abstract: In conclusion, backscattered power could be considered as a relevant parameter to quantify tumor necrosis in vivo.

Cited by 30 publications

References 16 publications

Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration

Dynamic assessment of antiangiogenic therapy by monitoring both tumoral vascularization and tissue degeneration

Metastatic Renal Cell Carcinoma Treated with Sunitinib: Early Evaluation of Treatment Response Using Dynamic Contrast-Enhanced Ultrasonography

Sunitinib therapy for metastatic renal cell carcinoma: recommendations for management of side effects

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