Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab

Lassau, Nathalie; Coiffier, B; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, M.; Taïeb, S.; Aziza, R.; Sarran, A.; Labbé-Devilliers, C.; Gallix, B.; Lucidarme, Olivier; Ptak, Y; Rocher, Laurence; Caquot, Louis Michel; Chagnon, S; Marion, D.; Luciani, Alain; Feutray, S.; Uzan-Augui, J.; Benatsou, Baya; Bonastre, Julia; Koscielny, Serge

doi:10.1093/annonc/mdw280

Cited by 28 publications

(27 citation statements)

References 18 publications

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“…As observed in Figure d , even in a homogenous controlled animal population, variability in the optimal gap was observed. Although no predictive biomarker has yet been clearly validated with anti‐angiogenics, our model parameters (possibly included in a broader modeling of metastatic disease) could be quantitatively linked to imaging data and/or predictive circulating biomarkers acting as covariates . Consequently, this would provide personalized simulations of response to treatment allowing to individually adapt the dose and timing in order to maximize the efficacy and reduce the toxicity at the patient's bedside.…”

Section: Discussionmentioning

confidence: 99%

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non‐Small Cell Lung Carcinoma

Imbs

Cheikh

Boyer

et al. 2017

CPT Pharmacom & Syst Pharma

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Concomitant administration of bevacizumab and pemetrexed‐cisplatin is a common treatment for advanced nonsquamous non‐small cell lung cancer (NSCLC). Vascular normalization following bevacizumab administration may transiently enhance drug delivery, suggesting improved efficacy with sequential administration. To investigate optimal scheduling, we conducted a study in NSCLC‐bearing mice. First, experiments demonstrated improved efficacy when using sequential vs. concomitant scheduling of bevacizumab and chemotherapy. Combining this data with a mathematical model of tumor growth under therapy accounting for the normalization effect, we predicted an optimal delay of 2.8 days between bevacizumab and chemotherapy. This prediction was confirmed experimentally, with reduced tumor growth of 38% as compared to concomitant scheduling, and prolonged survival (74 vs. 70 days). Alternate sequencing of 8 days failed in achieving a similar increase in efficacy, thus emphasizing the utility of modeling support to identify optimal scheduling. The model could also be a useful tool in the clinic to personally tailor regimen sequences.

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Section: Discussionmentioning

confidence: 99%

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non‐Small Cell Lung Carcinoma

Imbs

Cheikh

Boyer

et al. 2017

CPT Pharmacom & Syst Pharma

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“…Short-term rhES treatment induces a 'time window' of tumor vascular normalization. The 'time window' of tumor vascular normalization has been suggested to occur on days 4 to 6 following anti-angiogenic treatment; in most cases, maximum tumor vascular normalization occurred on day 7 (15,21). To examine the association between TSP-1 expression and vascular normalization, the vascular appearance, including the density and coverage of pericytes, in a SW620 xenograft tumor model was dynamically monitored.…”

Section: Resultsmentioning

confidence: 99%

“…The IFP of tumors can be monitored; however, a tissue puncture examination cannot be performed, as this may promote the metastasis of tumor cells. Recently, Lassau et al (15) used dynamic contrast enhanced ultrasonography to observe tumor vascular normalization. This method appeared to be suitable for clinical use for measuring the degree of tumor blood perfusion over time.…”

Section: Introductionmentioning

confidence: 99%

TSP‑1 as a novel biological marker of tumor vasculature normalization in colon carcinoma induced by Endostar

Yang

Fan

et al. 2020

Oncol Lett

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Blood vessels in tumors often exhibit abnormal morphology and function, which promotes the growth, metastasis and resistance of tumors to conventional therapies. Therefore, vascular normalization is an emerging strategy to enhance the effectiveness of radiotherapy and chemotherapy when used in combination; however, there is a lack of evidence regarding the optimal schedule for the co-administration of anti-angiogenic and chemotherapeutic drugs. Scheduling treatment is important as the period for normalization is transient, also known as the 'time window'; however, no biomarker has been identified to detect this window. In the present study, recombinant human endostatin (rhES) was employed as an anti-angiogenic agent in xenograft tumor tissue in mice. Following rhES or control (saline) treatment, the density and integrity of tumor vessels were detected by immunofluorescence staining for cluster of differentiation 31 and α-smooth muscle actin; the level of hypoxia in tumor tissue was examined by immunohistochemistry with pimonidazole; the necrotic area was evaluated by hematoxylin and eosin staining; and the level of thrombospondin-1 (TSP-1) in plasma was tested by ELISA. The Cell Counting Kit-8 assay was also used to evaluate the effect of rhES on the proliferation of colon carcinoma SW620 cells. A 'time window' normalized vasculature was determined between day 4 and 6 following rhES treatment, and accompanied by a decrease in hypoxia in tumor tissue. Decreasing plasma TSP-1 levels were consistent with changes in vascular morphology and hypoxia, which exhibited features of normalization. In addition, rhES had no effect on the proliferation of SW620 cells, suggesting that the reduction in TSP-1 was associated with increased oxygen content during vascular normalization, rather than inhibited cell proliferation. In conclusion, TSP-1 may be a potential biomarker for predicting the normalization window of colon cancer vessels.

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“…provided additional data on patients enrolled in their large French multicenter trial reported in 2014 [30]. They reported that a cutoff point of 12 s for the mTT measured at D7 was associated with an improved PFS for the 46 patients with colon cancer (p = 0.025).…”

Section: Discussionmentioning

confidence: 99%

Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases

Tranquart¹,

Dujardin

Bouché

et al. 2017

Ultraschall in Med

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Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab

Abstract: 2007-A00399-44.

Cited by 28 publications

References 18 publications

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non‐Small Cell Lung Carcinoma

Revisiting Bevacizumab + Cytotoxics Scheduling Using Mathematical Modeling: Proof of Concept Study in Experimental Non‐Small Cell Lung Carcinoma

TSP‑1 as a novel biological marker of tumor vasculature normalization in colon carcinoma induced by Endostar

Value of Contrast-Enhanced Ultrasound Quantification Criteria for Identifying Patients not Responding to Bevacizumab-Based Therapy for Colorectal Liver Metastases

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