European Radiology

, Volume 27, Issue 6, pp 2532–2537 | Cite as

Dual energy CT allows for improved characterization of response to antiangiogenic treatment in patients with metastatic renal cell cancer

  • K. Hellbach
  • A. Sterzik
  • W. Sommer
  • M. Karpitschka
  • N. Hummel
  • J. Casuscelli
  • M. Ingrisch
  • M. Schlemmer
  • A. Graser
  • Michael Staehler



To evaluate the potential role of dual energy CT (DECT) to visualize antiangiogenic treatment effects in patients with metastatic renal cell cancer (mRCC) while treated with tyrosine-kinase inhibitors (TKI).


26 patients with mRCC underwent baseline and follow-up single-phase abdominal contrast enhanced DECT scans. Scans were performed immediately before and 10 weeks after start of treatment with TKI. Virtual non-enhanced (VNE) and colour coded iodine images were generated. 44 metastases were measured at the two time points. Hounsfield unit (HU) values for VNE and iodine density (ID) as well as iodine content (IC) in mg/ml of tissue were derived. These values were compared to the venous phase DECT density (CTD) of the lesions. Values before and after treatment were compared using a paired Student’s t test.


Between baseline and follow up, mean CTD and DECT-derived ID both showed a significant reduction (p < 0.005). The relative reduction measured in percent was significantly greater for ID than for CTD (49.8 ± 36,3 % vs. 29.5 ± 20.8 %, p < 0.005). IC was also significantly reduced under antiangiogenic treatment (p < 0.0001).


Dual energy CT-based quantification of iodine content of mRCC metastases allows for significantly more sensitive and reproducible detection of antiangiogenic treatment effects.

Key Points

A sign of tumour response to antiangiogenic treatment is reduced tumour perfusion.

DECT allows visualizing iodine uptake, which serves as a marker for vascularization.

More sensitive detection of antiangiogenic treatment effects in mRCC is possible.


Metastatic renal cell carcinoma Therapy monitoring Response evaluation Antiangiogenic treatment Dual energy computed tomography 

Abbreviations and acronyms




Dual energy CT density (venous phase)


Dual energy computed tomography


Dose-length product


Follow up


Gastrointestinal stromal tumours


Hounsfield unit


Iodine concentration


Iodine density


Iodine related attenuation


(metastatic) renal cell cancer


Region of interest


Tyrosine-kinase inhibitor


Vascular endothelial growth factor


Virtual non-enhanced



The scientific guarantor of this publication is Michael Staehler, MD, PhD. The authors of this manuscript declare relationships with the following companies: Bayer, Braco, GSK, Novartis, Pfizer, and Roche. The authors state that this work has not received any funding. No complex statistical methods were necessary for this paper. Institutional Review Board approval was obtained. Written informed consent was obtained from all subjects (patients) in this study. No study subjects or cohorts have been previously reported. Methodology: prospective, case-control study, performed at one institution.


  1. 1.
    Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C (2008) Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 34:193–205CrossRefPubMedGoogle Scholar
  2. 2.
    Janzen NK, Kim HL, Figlin RA, Belldegrun AS (2003) Surveillance after radical or partial nephrectomy for localized renal cell carcinoma and management of recurrent disease. Urol Clin N Am 30:843–852CrossRefGoogle Scholar
  3. 3.
    Ljungberg B, Campbell SC, Choi HY et al (2011) The epidemiology of renal cell carcinoma. Eur Urol 60:615–621CrossRefPubMedGoogle Scholar
  4. 4.
    Athar U, Gentile TC (2008) Treatment options for metastatic renal cell carcinoma: a review. Can J Urol 15:3954–3966PubMedGoogle Scholar
  5. 5.
    Aslam S, Eisen T (2013) Vascular endothelial growth factor receptor tyrosine kinase inhibitors in metastatic renal cell cancer: latest results and clinical implications. Ther Adv Med Oncol 5:324–333CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefPubMedGoogle Scholar
  7. 7.
    Brufau BP (2013) Metastatic renal cell carcinoma: radiologic findings and assessment of response to targeted antiangiogenic therapy by using multidetector CT. Radiographics 33:1691–1716CrossRefPubMedGoogle Scholar
  8. 8.
    Choi H, Cerqueda CS, Villalba LB, Izquierdo RS, Gonzales BM, Molina CN (2008) Response evaluation of gastrointestinal stromal tumors. Oncologist 13:4–7CrossRefPubMedGoogle Scholar
  9. 9.
    Graser A, Becker CR, Staehler M (2010) Single-phase dual-energy CT allows for characterization of renal masses as benign or malignant. Investig Radiol 45:399–405Google Scholar
  10. 10.
    Johnson TR (2012) Dual-energy CT: general principles. AJR Am J Roentgenol 199:S3–S8CrossRefPubMedGoogle Scholar
  11. 11.
    Graser A, Johnson TR, Chandarana H, Macari M (2009) Dual energy CT: preliminary observations and potential clinical applications in the abdomen. Eur Radiol 19:13–23CrossRefPubMedGoogle Scholar
  12. 12.
    Lee JA, Jeong WK, Kim Y (2013) Dual-energy CT to detect recurrent HCC after TACE: initial experience of color-coded iodine CT imaging. Eur J Radiol 82:569–576CrossRefPubMedGoogle Scholar
  13. 13.
    Apfaltrer P, Meyer M, Meier C et al (2012) Contrast-enhanced dual-energy CT of gastrointestinal stromal tumors: is iodine-related attenuation a potential indicator of tumor response? Investig Radiol 47:65–70CrossRefGoogle Scholar
  14. 14.
    Meyer M, Hohenberger P, Apfaltrer P et al (2013) CT-based response assessment of advanced gastrointestinal stromal tumor: dual energy CT provides a more predictive imaging biomarker of clinical benefit than RECIST or Choi criteria. Eur J Radiol 82:923–928CrossRefPubMedGoogle Scholar
  15. 15.
    Tawfik AM, Kerl JM, Razek AA (2011) Image quality and radiation dose of dual-energy CT of the head and neck compared with a standard 120-kVp acquisition. AJNR Am J Neuroradiol 32:1994–1999CrossRefPubMedGoogle Scholar
  16. 16.
    Stiller W, Schwarzwaelder CB, Sommer CM, Veloza S, Radeleff BA, Kauczor HU (2012) Dual-energy, standard and low-kVp contrast-enhanced CT-cholangiography: a comparative analysis of image quality and radiation exposure. Eur J Radiol 81:1405–1412CrossRefPubMedGoogle Scholar
  17. 17.
    Atzpodien J, Schmitt E, Gertenbach U et al (2005) Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: results of a prospectively randomised trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN). Br J Cancer 92:843–846CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Hudes G, Carducci M, Tomczak P et al (2007) Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N Engl J Med 356:2271–2281CrossRefPubMedGoogle Scholar
  19. 19.
    Jonasch E, Corn P, Pagliaro LC et al (2010) Upfront, randomized, phase 2 trial of sorafenib versus sorafenib and low-dose interferon alfa in patients with advanced renal cell carcinoma: clinical and biomarker analysis. Cancer 116:57–65PubMedPubMedCentralGoogle Scholar
  20. 20.
    Motzer RJ, Rini BI, Bukowski RM et al (2006) Sunitinib in patients with metastatic renal cell carcinoma. JAMA 295:2516–2524CrossRefPubMedGoogle Scholar
  21. 21.
    Bex A, Fournier L, Lassau N et al (2014) Assessing the response to targeted therapies in renal cell carcinoma: technical insights and practical considerations. Eur Urol 65:766–777CrossRefPubMedGoogle Scholar
  22. 22.
    Choueiri TK (2011) VEGF inhibitors in metastatic renal cell carcinoma: current therapies and future perspective. Curr Clin Pharmacol 6:164–168CrossRefPubMedGoogle Scholar
  23. 23.
    Lv P, Liu J, Yan X et al (2016) CT spectral imaging for monitoring the therapeutic efficacy of VEGF receptor kinase inhibitor AG-013736 in rabbit VX2 liver tumours. Eur RadiolGoogle Scholar
  24. 24.
    Uhrig M, Sedlmair M, Schlemmer HP, Hassel JC, Ganten M (2013) Monitoring targeted therapy using dual-energy CT: semi-automatic RECIST plus supplementary functional information by quantifying iodine uptake of melanoma metastases. Cancer Imaging 13:306–313CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Dai X, Schlemmer HP, Schmidt B et al (2013) Quantitative therapy response assessment by volumetric iodine-uptake measurement: initial experience in patients with advanced hepatocellular carcinoma treated with sorafenib. Eur J Radiol 82:327–334CrossRefPubMedGoogle Scholar
  26. 26.
    Baxa J, Matouskova T, Krakorova G et al (2015) Dual-phase dual-energy CT in patients treated with erlotinib for advanced non-small cell lung cancer: possible benefits of iodine quantification in response assessment. Eur RadiolGoogle Scholar
  27. 27.
    Song KD, Kim CK, Park BK, Kim B (2011) Utility of iodine overlay technique and virtual unenhanced images for the characterization of renal masses by dual-energy CT. AJR 197:1076–1082CrossRefGoogle Scholar
  28. 28.
    Helck A, Hummel N, Meinel FG, Johnson T, Nikolaou K, Graser A et al (2014) Can single-phase dual-energy CT reliably identify adrenal adenomas? Eur Radiol 24:1636–1642CrossRefPubMedGoogle Scholar
  29. 29.
    Mileto A, Sofue K, Marin D (2016) Imaging the renal lesion with dual-energy multidetector CT and multi-energy applications in clinical practice: what can it truly do for you? Eur RadiolGoogle Scholar
  30. 30.
    Park SY, Kim CK, Park BK (2014) Dual-energy CT in assessing therapeutic response to radiofrequency ablation of renal cell carcinomas. Eur J Radiol 83:73–79CrossRefGoogle Scholar
  31. 31.
    Tsapaki V, Aldrich JE, Sharma R et al (2006) Dose reduction in CT while maintaining diagnostic confidence: diagnostic reference levels at routine head, chest, and abdominal CT--IAEA-coordinated research project. Radiology 240:828–834CrossRefPubMedGoogle Scholar
  32. 32.
    Wichmann JL, Hardie AD, Schoepf UJ et al (2016) Single- and dual-energy CT of the abdomen: comparison of radiation dose and image quality of 2nd and 3rd generation dual-source CT. Eur RadiolGoogle Scholar

Copyright information

© European Society of Radiology 2016

Authors and Affiliations

  • K. Hellbach
    • 1
  • A. Sterzik
    • 1
  • W. Sommer
    • 1
  • M. Karpitschka
    • 1
  • N. Hummel
    • 1
  • J. Casuscelli
    • 2
  • M. Ingrisch
    • 1
  • M. Schlemmer
    • 3
  • A. Graser
    • 1
  • Michael Staehler
    • 2
  1. 1.Department of Clinical RadiologyLudwig-Maximilians-University Hospital MunichMünchenGermany
  2. 2.Department of UrologyLudwig-Maximilians-University Hospital MunichMünchenGermany
  3. 3.Department of Palliative CareKrankenhaus Barmherzige Brüder MünchenMünchenGermany

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