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Assessment of the extracellular volume fraction for the grading of clear cell renal cell carcinoma: first results and histopathological findings

  • Magnetic Resonance
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Abstract

Objectives

To assess the potential of T1 mapping–based extracellular volume fraction (ECV) for the identification of higher grade clear cell renal cell carcinoma (cRCC), based on histopathology as the reference standard.

Methods

For this single-center, institutional review board–approved prospective study, 27 patients (17 men, median age 62 ± 12.4 years) with pathologic diagnosis of cRCC (nucleolar International Society of Urological Pathology (ISUP) grading) received abdominal MRI scans at 1.5 T using a modified Look-Locker inversion recovery (MOLLI) sequence between January 2017 and June 2018. Quantitative T1 values were measured at different time points (pre- and postcontrast agent administration) and quantification of the ECV was performed on MRI and histological sections (H&E staining).

Results

Reduction in T1 value after contrast agent administration and MR-derived ECV were reliable predictors for differentiating higher from lower grade cRCC. Postcontrast T1diff values (T1diff = T1 difference between the native and nephrogenic phase) and MR-derived ECV were significantly higher for higher grade cRCC (ISUP grades 3–4) compared with lower grade cRCC (ISUP grades 1–2) (p < 0.001). A cutoff value of 700 ms could distinguish higher grade from lower grade tumors with 100% (95% CI 0.69–1.00) sensitivity and 82% (95% CI 0.57–0.96) specificity. There was a positive and strong correlation between MR-derived ECV and histological ECV (p < 0.01, r = 0.88). Interobserver agreement for quantitative longitudinal relaxation times in the T1 maps was excellent.

Conclusions

T1 mapping with ECV measurement could represent a novel in vivo biomarker for the classification of cRCC regarding their nucleolar grade, providing incremental diagnostic value as a quantitative MR marker.

Key Points

• Reduction in MRI T1 relaxation times after contrast agent administration and MR-derived extracellular volume fraction are useful parameters for grading of clear cell renal cell carcinoma (cRCC).

• T1 differences between the native and the nephrogenic phase are higher for higher grade cRCC compared with lower grade cRCC and MRI-derived extracellular volume fraction (ECV) and histological ECV show a strong correlation.

• T1 mapping with ECV measurement may be helpful for the noninvasive assessment of cRCC pathology, being a safe and feasible method, and it has potential to optimize individualized treatment options, e.g., in the decision of active surveillance.

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Abbreviations

ADC:

Apparent diffusion coefficient

AUA:

American Urological Association

cRCC:

Clear cell renal cell carcinoma

DWI:

Diffusion-weighted imaging

ECM:

Extracellular matrix

ECV:

Extracellular volume fraction

ESM:

Electronic supplementary material

H&E:

Hematoxylin and eosin

ICC:

Intraclass coefficient

ISUP:

International Society of Urological Pathology

MOLLI:

Modified Look-Locker inversion recovery

ROC:

Receiver operating characteristic curve

ROI:

Region of interest

SNR:

Signal-to-noise ratio

TER:

Tumor enhancement ratio

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Acknowledgements

LCA and BR are grateful for their participation in the BIH Charité - Junior Clinician Scientist Program funded by the Charité - Universitaetsmedizin Berlin and the Berlin Institute of Health. JB is participant in the BIH – Twinning Grant Program funded by the Charité - Universitaetsmedizin Berlin and the Berlin Institute of Health. MRM is funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – SFB 1340/1 2018, 5943/31/41.

Funding

The authors state that this work has not received any funding.

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Authors and Affiliations

  1. Department of Radiology, Charité, Charitéplatz 1, 10117, Berlin, Germany

    Lisa C. Adams, Ute L. Fahlenkamp, Guenther Engel, Stefan Siepmann, Moritz Wagner, Bernd Hamm & Marcus R. Makowski

  2. Department of Pathology, Charité, Charitéplatz 1, 10117, Berlin, Germany

    Philipp Jurmeister

  3. Department of Urology, Charité, Charitéplatz 1, 10117, Berlin, Germany

    Bernhard Ralla & Jonas Busch

  4. Department of Radiology, Charité, Hindenburgdamm 30, 12203, Berlin, Germany

    Keno K. Bressem

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  1. Lisa C. Adams
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Corresponding author

Correspondence to Lisa C. Adams.

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Guarantor

The scientific guarantor of this publication is Lisa C. Adams.

Conflict of interest

The authors of this manuscript declare relationships with the following companies: Bernd Hamm has received research grants for the Department of Radiology, Charité – Universitätsmedizin Berlin from the following companies: 1. Abbott, 2. Actelion Pharmaceuticals, 3. Bayer Schering Pharma, 4. Bayer Vital, 5. BRACCO Group, 6. Bristol-Myers Squibb, 7. Charite research organisation GmbH, 8. Deutsche Krebshilfe, 9. Dt. Stiftung für Herzforschung, 10. Essex Pharma, 11. EU Programmes, 12. Fibrex Medical Inc., 13. Focused Ultrasound Surgery Foundation, 14. Fraunhofer Gesellschaft, 15. Guerbet, 16. INC Research, 17. lnSightec Ud., 18. IPSEN Pharma, 19. Kendlel MorphoSys AG, 20. Lilly GmbH, 21. Lundbeck GmbH, 22. MeVis Medical Solutions AG, 23. Nexus Oncology, 24. Novartis, 25. Parexel Clinical Research Organisation Service, 26. Perceptive, 27. Pfizer GmbH, 28. Philipps, 29. Sanofis-Aventis S.A, 30. Siemens, 31. Spectranetics GmbH, 32. Terumo Medical Corporation, 33. TNS Healthcare GMbH, 34. Toshiba, 35. UCB Pharma, 36. Wyeth Pharma, 37. Zukunftsfond Berlin (TSB), 38. Amgen, 39. AO Foundation, 40. BARD, 41. BBraun, 42. Boehring Ingelheimer, 43. Brainsgate, 44. PPD (Clinical Research Organisation), 45. CELLACT Pharma, 46. Celgene, 47. CeloNova BioSciences, 48. Covance, 49. DC Deviees, Ine. USA, 50. Ganymed, 51. Gilead Sciences, 52. Glaxo Smith Kline, 53. ICON (Clinical Research Organisation), 54. Jansen, 55. LUX Bioseienees, 56. MedPass, 57. Merek, 58. Mologen, 59. Nuvisan, 60. Pluristem, 61. Quintiles, 62. Roehe, 63. Sehumaeher GmbH (Sponsoring eines Workshops), 64. Seattle Geneties, 65. Symphogen, 66. TauRx Therapeuties Ud., 67. Accovion, 68. AIO: Arbeitsgemeinschaft Internistische Onkologie, 69. ASR Advanced sleep research, 70. Astellas, 71. Theradex, 72. Galena Biopharma, 73. Chiltern, 74. PRAint, 75. lnspiremd, 76. Medronic, 77. Respicardia, 78. Silena Therapeutics, 79. Spectrum Pharmaceuticals, 80. St. Jude., 81. TEVA, 82. Theorem, 83. Abbvie, 84. Aesculap, 85. Biotronik, 86. Inventivhealth, 87. ISA Therapeutics, 88. LYSARC, 89. MSD, 90. novocure, 91. Ockham oncology, 92. Premier-research, 93. Psi-cro, 94. Tetec-ag, 94. Tetec-ag, 95. Winicker-norimed, 96. Achaogen Inc, 97. ADIR, 98. AstraZenaca AB, 99. Demira Inc, 100. Euroscreen S.A., 101. Galmed Research and Development Ltd., 102. GETNE, 103. Guidant Europe NV, 104. Holaira Inc., 105. Immunomedics Inc., 106. Innate Pharma, 107. Isis Pharmaceuticals Inc, 108. Kantar Health GmbH, 109. MedImmune Inc, 110. Medpace Germany GmbH (CRO), 111. Merrimack Pharmaceuticals Inc, 112. Millenium Pharmaceuticals Inc, 113. Orion Corporation Orion Pharma, 114. Pharmacyclics Inc, 115. PIQUR Therapeutics Ltd, 116. Pulmonx International Sárl, 117. Servier (CRO), 118. SGS Life Science Services (CRO), 119. Treshold Pharmaceuticals Inc. There are no patents, products in development or marketed products to declare. This does not alter the authors’ adherence to all the European Radiology policies on sharing data and materials.

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No complex statistical methods were necessary for this paper.

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Written informed consent was obtained from all patients in this study.

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Institutional Review Board approval was obtained.

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• diagnostic or prognostic study (proof-of-concept study)

• performed at one institution

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Adams, L.C., Jurmeister, P., Ralla, B. et al. Assessment of the extracellular volume fraction for the grading of clear cell renal cell carcinoma: first results and histopathological findings. Eur Radiol 29, 5832–5843 (2019). https://doi.org/10.1007/s00330-019-06087-x

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