Dataset Information

Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion.

ABSTRACT: PURPOSE:Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. METHODS:A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. RESULTS:At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p?=?0.014), hypoxic fraction (-0.60, p?=?0.025) and TBR (-0.56, p?=?0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53?±?36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15?±?17 % and 28?±?28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. CONCLUSION:The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia.

SUBMITTER: van Elmpt W

PROVIDER: S-EPMC4700090 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion.

van Elmpt Wouter W Zegers Catharina M L CML Reymen Bart B Even Aniek J G AJG Dingemans Anne-Marie C AC Oellers Michel M Wildberger Joachim E JE Mottaghy Felix M FM Das Marco M Troost Esther G C EGC Lambin Philippe P

European journal of nuclear medicine and molecular imaging 20150904 2

<h4>Purpose</h4>Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level.<h4>Methods</h4>A group of 14 NSCL ...[more]

PMID: 26338178

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Project description:Preclinical studies have shown a larger inhibition of tumour growth when exercise begins prior to tumour implant (preventative setting) than when training begins after tumour implant (therapeutic setting). However, post-implantation exercise may alter the tumour microenvironment to make it more vulnerable to treatment by increasing tumour perfusion while reducing hypoxia. This has been shown most convincingly in breast and prostate cancer models to date and it is unclear whether other tumour types respond in a similar way. We aimed to determine whether tumour perfusion and hypoxia are altered with exercise in a melanoma model, and compared this with a breast cancer model. We hypothesised that post-implantation exercise would reduce tumour hypoxia and increase perfusion in these two models. Female, 6-10 week old C57BL/6 mice were inoculated with EO771 breast or B16-F10 melanoma tumour cells before randomisation to either exercise or non-exercising control. Exercising mice received a running wheel with a revolution counter. Mice were euthanised when tumours reached maximum ethical size and the tumours assessed for perfusion, hypoxia, blood vessel density and proliferation. We saw an increase in heart to body weight ratio in exercising compared with non-exercising mice (p = 0.0008), indicating that physiological changes occurred with this form of physical activity. However, exercise did not affect vascularity, perfusion, hypoxia or tumour growth rate in either tumour type. In addition, EO771 tumours had a more aggressive phenotype than B16-F10 tumours, as inferred from a higher rate of proliferation (p<0.0001), a higher level of tumour hypoxia (p = 0.0063) and a higher number of CD31+ vessels (p = 0.0005). Our results show that although a physiological training effect was seen with exercise, it did not affect tumour hypoxia, perfusion or growth rate. We suggest that exercise monotherapy is minimally effective and that future preclinical work should focus on the combination of exercise with standard cancer therapies.

Project description:PURPOSE:To correlate semiquantitative parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for non-small cell lung cancer (NSCLC). METHODS AND MATERIALS:Twenty-four NSCLC patients who underwent pretreatment 18F-FDG-PET and DCE-MRI were analyzed. The maximum standardized uptake value (SUVmax) was measured from 18F-FDG-PET. Dynamic contrast-enhanced MRI was obtained on a 3T MRI scanner using 4-dimensional T1-weighted high-resolution imaging with a volume excitation sequence. The DCE-MRI parameters, consisting of mean, median, standard deviation (SD), and median absolute deviation (MAD) of peak enhancement, time to peak (TTP), time to half peak (TTHP), wash-in slope (WIS), wash-out slope (WOS), initial gradient, wash-out gradient, signal enhancement ratio, and initial area under the relative signal enhancement curve taken up to 30, 60, 90, 120, 150, and 180 seconds, TTP, and TTHP (IAUCtthp), were calculated for each lesion. Univariate analysis (UVA) was performed using Spearman correlation. A linear regression model to predict SUVmax from DCE-MRI parameters was developed by multivariate analysis (MVA) using least absolute shrinkage selection operator in combination with leave-one-out cross-validation (LOOCV). RESULTS:In UVA, mean(WOS) (? = -0.456, P = .025), mean(IAUCtthp) (? = -0.439, P = .032), median(IAUCtthp) (? = -0.543, P = .006), and MAD(IAUCtthp) (? = -0.557, P = .005) were statistically significant; all these parameters were negatively correlated with SUVmax. In MVA, a linear combination of SD(WIS), SD(TTP), MAD(TTHP), and MAD(IAUCtthp) was statistically significant for predicting SUVmax (LOOCV-based adjusted R2 = 0.298, P = .0006). A decrease in SD(WIS), MAD(TTHP), and MAD(IAUCtthp) and an increase in SD(TTP) were associated with a significant increase in SUVmax. CONCLUSION:An association was found between SUVmax, the SD, and MAD of DCE-MRI metrics derived during contrast uptake in NSCLC, reflecting that intratumoral heterogeneity in wash-in contrast kinetics is associated with tumor metabolism. Although MAD(IAUCtthp) was a significant feature in both UVA and MVA, the LASSO-based multivariate regression model yielded better predictability of SUVmax than a univariate regression model using MAD(IAUCtthp). This study will facilitate understanding of the complex relationship between tumor vascularization and metabolism and eventually help in guiding targeted therapy.

Dataset Information

Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion.

Publications

Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion.

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