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Dynamic contrast-enhanced computed tomography to assess early activity of cetuximab in squamous cell carcinoma of the head and neck.

Schmitz S, Rommel D, Michoux N, Lhommel R, Hanin FX, Duprez T, Machiels JP - Radiol Oncol (2015)

Bottom Line: A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS).Significant correlations were found between DCE parameters and the other two modalities.Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology and Head and Neck Surgery, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT

Background: Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN).

Methods: Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow Fp, extravascular space ve, vascular space vp, and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points.

Results: Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion.

Conclusions: Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome.

No MeSH data available.


Related in: MedlinePlus

Example of time intensity curves derived from the internal carotid and tumoral lesion before (A) and during treatment with cetuximab (B) in a patient with a squamous cell carcinoma of the head and neck. The quality of the fits of TICs using the Brix two-compartment kinetic model was found to be good (estimation of the root mean squared error of the regression averaged on the 14 normalized fits: εpre-treatment = 5%, εduring-treatment = 6%).
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f2-rado-49-01-17: Example of time intensity curves derived from the internal carotid and tumoral lesion before (A) and during treatment with cetuximab (B) in a patient with a squamous cell carcinoma of the head and neck. The quality of the fits of TICs using the Brix two-compartment kinetic model was found to be good (estimation of the root mean squared error of the regression averaged on the 14 normalized fits: εpre-treatment = 5%, εduring-treatment = 6%).

Mentions: The software Image J (processing program developed by the National Institutes of Health, http://rsbweb.nih.gov/ij/) was used to segment the regions of interest (ROI). An expert head and neck radiologist manually drew the ROI which included the internal carotid (for the arterial input function calculation) and the whole tumor (Figure 2).


Dynamic contrast-enhanced computed tomography to assess early activity of cetuximab in squamous cell carcinoma of the head and neck.

Schmitz S, Rommel D, Michoux N, Lhommel R, Hanin FX, Duprez T, Machiels JP - Radiol Oncol (2015)

Example of time intensity curves derived from the internal carotid and tumoral lesion before (A) and during treatment with cetuximab (B) in a patient with a squamous cell carcinoma of the head and neck. The quality of the fits of TICs using the Brix two-compartment kinetic model was found to be good (estimation of the root mean squared error of the regression averaged on the 14 normalized fits: εpre-treatment = 5%, εduring-treatment = 6%).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4362602&req=5

f2-rado-49-01-17: Example of time intensity curves derived from the internal carotid and tumoral lesion before (A) and during treatment with cetuximab (B) in a patient with a squamous cell carcinoma of the head and neck. The quality of the fits of TICs using the Brix two-compartment kinetic model was found to be good (estimation of the root mean squared error of the regression averaged on the 14 normalized fits: εpre-treatment = 5%, εduring-treatment = 6%).
Mentions: The software Image J (processing program developed by the National Institutes of Health, http://rsbweb.nih.gov/ij/) was used to segment the regions of interest (ROI). An expert head and neck radiologist manually drew the ROI which included the internal carotid (for the arterial input function calculation) and the whole tumor (Figure 2).

Bottom Line: A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS).Significant correlations were found between DCE parameters and the other two modalities.Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology and Head and Neck Surgery, Cliniques Universitaires Saint-Luc and Institut de Recherche Clinique et Expérimentale (Pole MIRO), Université Catholique de Louvain, Brussels, Belgium.

ABSTRACT

Background: Cetuximab, a monoclonal antibody targeting the Epidermal Growth Factor Receptor (EGFR), has demonstrated activity in various tumor types. Using dynamic contrast-enhanced computed tomography (DCE-CT), we investigated the early activity of cetuximab monotherapy in previously untreated patients with squamous cell carcinoma of the head and neck (SCCHN).

Methods: Treatment-naïve patients with SCCHN received cetuximab for 2 weeks before curative surgery. Treatment activity was evaluated by DCE-CT at baseline and before surgery. Tumor vascular and interstitial characteristics were evaluated using the Brix two-compartment kinetic model. Modifications of the perfusion parameters (blood flow Fp, extravascular space ve, vascular space vp, and transfer constant PS) were assessed between both time points. DCE data were compared to FDG-PET and histopathological examination obtained simultaneously. Plasmatic vascular markers were investigated at different time points.

Results: Fourteen patients had evaluable DCE-CT parameters at both time points. A significant increase in the extravascular extracellular space ve accessible to the tracer was observed but no significant differences were found for the other kinetic parameters (Fp, vp or PS). Significant correlations were found between DCE parameters and the other two modalities. Plasmatic VEGF, PDGF-BB and IL-8 decreased as early as 2 hours after cetuximab infusion.

Conclusions: Early activity of cetuximab on tumor interstitial characteristics was detected by DCE-CT. Modifications of plasmatic vascular markers are not sufficient to confirm anti-angiogenic cetuximab activity in vivo. Further investigation is warranted to determine to what extent DCE-CT parameters are modified and to evaluate whether they are able to predict treatment outcome.

No MeSH data available.


Related in: MedlinePlus