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

Wouter van Elmpt; Catharina M.L. Zegers; Bart Reymen; Aniek J.G. Even; Anne Marie C. Dingemans; Michel Oellers; Joachim E. Wildberger; Felix M. Mottaghy; Marco Das; Esther G.C. Troost; Philippe Lambin

doi:10.1007/s00259-015-3169-4

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

Wouter van Elmpt^*, Catharina M.L. Zegers, Bart Reymen, Aniek J.G. Even, Anne Marie C. Dingemans, Michel Oellers, Joachim E. Wildberger, Felix M. Mottaghy, Marco Das, Esther G.C. Troost, Philippe Lambin

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Pages (from-to)	240-248
Number of pages	9
Journal	European Journal of Nuclear Medicine and Molecular Imaging
Volume	43
Issue number	2
DOIs	https://doi.org/10.1007/s00259-015-3169-4
Publication status	Published - Feb 2016
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2015, The Author(s).

Funding:
The authors acknowledge financial support from the EU 7th
Framework Program (ARTFORCE), Kankeronderzoekfonds Limburg
from the Health Foundation Limburg and the Dutch Cancer Society (KWF MAC 2011-5020 and KWF MAC 2011-4970). This research
was also supported by the Dutch Technology Foundation STW (grant
no. 10696 DuCAT), which is the applied science division of NWO, and
the Technology Programme of the Ministry of Economic Affairs.

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Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer quantification of tumour hypoxia, metabolism and perfusionFinal published version, 1.3 MBLicence: CC BY

Cite this

van Elmpt, W., Zegers, C. M. L., Reymen, B., Even, A. J. G., Dingemans, A. M. C., Oellers, M., Wildberger, J. E., Mottaghy, F. M., Das, M., Troost, E. G. C., & Lambin, P. (2016). Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion. European Journal of Nuclear Medicine and Molecular Imaging, 43(2), 240-248. https://doi.org/10.1007/s00259-015-3169-4

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title = "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.",

author = "{van Elmpt}, Wouter and Zegers, {Catharina M.L.} and Bart Reymen and Even, {Aniek J.G.} and Dingemans, {Anne Marie C.} and Michel Oellers and Wildberger, {Joachim E.} and Mottaghy, {Felix M.} and Marco Das and Troost, {Esther G.C.} and Philippe Lambin",

note = "Publisher Copyright: {\textcopyright} 2015, The Author(s). Funding: The authors acknowledge financial support from the EU 7th Framework Program (ARTFORCE), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF MAC 2011-5020 and KWF MAC 2011-4970). This research was also supported by the Dutch Technology Foundation STW (grant no. 10696 DuCAT), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs.",

year = "2016",

month = feb,

doi = "10.1007/s00259-015-3169-4",

language = "English",

volume = "43",

pages = "240--248",

journal = "European Journal of Nuclear Medicine and Molecular Imaging",

issn = "1619-7070",

publisher = "Springer-Verlag",

number = "2",

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van Elmpt, W, Zegers, CML, Reymen, B, Even, AJG, Dingemans, AMC, Oellers, M, Wildberger, JE, Mottaghy, FM, Das, M, Troost, EGC & Lambin, P 2016, 'Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion', European Journal of Nuclear Medicine and Molecular Imaging, vol. 43, no. 2, pp. 240-248. https://doi.org/10.1007/s00259-015-3169-4

Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion. / van Elmpt, Wouter; Zegers, Catharina M.L.; Reymen, Bart et al.
In: European Journal of Nuclear Medicine and Molecular Imaging, Vol. 43, No. 2, 02.2016, p. 240-248.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer

T2 - quantification of tumour hypoxia, metabolism and perfusion

AU - van Elmpt, Wouter

AU - Zegers, Catharina M.L.

AU - Reymen, Bart

AU - Even, Aniek J.G.

AU - Dingemans, Anne Marie C.

AU - Oellers, Michel

AU - Wildberger, Joachim E.

AU - Mottaghy, Felix M.

AU - Das, Marco

AU - Troost, Esther G.C.

AU - Lambin, Philippe

N1 - Publisher Copyright: © 2015, The Author(s). Funding: The authors acknowledge financial support from the EU 7th Framework Program (ARTFORCE), Kankeronderzoekfonds Limburg from the Health Foundation Limburg and the Dutch Cancer Society (KWF MAC 2011-5020 and KWF MAC 2011-4970). This research was also supported by the Dutch Technology Foundation STW (grant no. 10696 DuCAT), which is the applied science division of NWO, and the Technology Programme of the Ministry of Economic Affairs.

PY - 2016/2

Y1 - 2016/2

N2 - 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.

AB - 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.

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DO - 10.1007/s00259-015-3169-4

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SN - 1619-7070

VL - 43

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JO - European Journal of Nuclear Medicine and Molecular Imaging

JF - European Journal of Nuclear Medicine and Molecular Imaging

IS - 2

ER -

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

Abstract

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